InteractiveFly: GeneBrief

M6: Biological Overview | References

Tricellular junctions (TCJs) seal epithelial cell vertices and are essential for tissue integrity and physiology, but how TCJs are assembled and maintained is poorly understood. In Drosophila, the transmembrane proteins Anakonda (Aka, also known as Bark), Gliotactin (Gli) and M6 organize occluding TCJs. Aka and M6 localize in an interdependent manner to vertices and act jointly to localize Gli, but how these proteins interact to assemble TCJs was not previously known. This study shows that the proteolipid protein M6 physically interacts with Aka and with itself, and that M6 is palmitoylated on conserved juxta-membrane cysteine residues. This modification promotes vertex localization of M6 and binding to Aka, but not to itself, and becomes essential when TCJ protein levels are reduced. Abolishing M6 palmitoylation leads to delayed localization of M6 and Aka but does not affect the rate of TCJ growth or mobility of M6 or Aka. These findings suggest that palmitoylation-dependent recruitment of Aka by M6 promotes initiation of TCJ assembly, whereas subsequent TCJ growth relies on different mechanisms that are independent of M6 palmitoylation (Schleutker, 2024).

How specialized junctional complexes with distinct adhesive and occluding properties are built at three-cell contacts remains a fundamental open question in epithelial biology. Three TCJ-specific proteins, Aka, Gli and M6, are known in Drosophila, but how they interact to assemble TCJs was not known. This study reports insights into the early steps of TCJ assembly, which depends on interactions between the transmembrane proteins Aka and M6. It was first shown that all M6 isoforms share the elements required for vertex localization. Second, it was demonstrated that M6 is palmitoylated on a conserved cysteine cluster and that this modification is required for efficient initial localization of M6 to vertices, but not for subsequent TCJ growth and maintenance, indicating that different mechanisms control the early and late phases, respectively, of TCJ formation. Third, it was shown that Aka interacts with M6 in a palmitoylation-dependent manner, whereas M6 interacts with itself independently of palmitoylation, possibly forming homotypic clusters like the mammalian M6 homolog GPM6a (Schleutker, 2024).

These findings provide a molecular basis for the interdependent localization of Aka and M6 at TCJs, although it is not yet clear which physical or chemical features of vertices mediate localization of proteins to these sites. Aka engages in homotypic trans-interactions that depend on its expression in three adjacent cells and on its large extracellular domain, but not on its cytoplasmic domain, for accumulating at vertices. This suggests that the specific geometry of vertices or the presence of three adjacent plasma membranes act to recruit or maintain Aka localization. M6 is required for vertex localization of Aka in a permissive fashion (Wittek, 2020). These findings suggest possible mechanisms underlying this role. In one scenario, M6 might stabilize Aka in the plasma membrane by preventing its internalization. Supporting this idea is the finding that in the absence of M6 Aka was barely detectable at the plasma membrane but instead distributed throughout the cytoplasm (Wittek, 2020). Alternatively, association with M6 might concentrate Aka in a vertex-specific plasma membrane domain and thereby facilitate trans-interactions between Aka molecules on adjacent cells. This is reminiscent of the role of tetraspanins, which interact laterally among themselves and with other proteins to form large assemblies called tetraspanin-enriched microdomains (TEMs) or a tetraspanin web that controls the clustering and activity of TM proteins, such as EGFR or integrins (Schleutker, 2024).

S-palmitoylation was identified as a post-translational modification, which, although not essential for vertex localization of M6 or for TCJ formation, significantly enhances the efficiency and robustness of this process. Supporting this notion, palmitoylation of M6 becomes essential for TCJ formation and viability under conditions of reduced TCJ protein concentration. How could palmitoylation promote targeting of M6 to vertices? In many TM proteins, including claudins, tetraspanins and mammalian GPM6a, palmitoylation of juxtamembrane cysteine residues mediates association with cholesterol-rich membrane domains. Negative plasma membrane curvature at vertices might favor accumulation of cholesterol and could thereby attract palmitoylated proteins. Consistent with this idea, methyl-%beta;-cyclodextrin-induced depletion of cholesterol from the plasma membrane impaired the vertex localization of palmitoylated angulin-1 in cultured mammalian cells, although direct evidence for elevated cholesterol levels at cell vertices is lacking thus far (Schleutker, 2024).

Lack of M6 palmitoylation reduces, although it does not completely abolish, its interaction with Aka, resulting in delayed accumulation of M6 and Aka at vertices. How could palmitoylation affect the interaction of M6 with Aka? Structural predictions using AlphaFold and PPM3 (Predicting Protein position in Membranes) suggest that M6 protein adopts a tilted orientation in the membrane. Palmitoylation of the juxtamembrane cysteine cluster could stabilize the tilt and help to resolve a potential hydrophobic mismatch resulting from the different lengths of the four TMDs, thereby promoting a confirmation of M6 that is favorable for interaction with Aka. Palmitoylation of LRP6 has been proposed to act in this way by resolving a hydrophobic mismatch that otherwise causes the protein to be retained in the ER. Similarly, tetraspanins (e.g. CD151), require palmitoylation for interaction with other TM proteins (Schleutker, 2024).

Intriguingly, eliminating palmitoylation of M6 revealed a distinct requirement of this modification for efficient initial accumulation of M6 at vertex tips, whereas the subsequent extension of these clusters along the apical-basal vertex axis apparently relies on a different mechanism. This might include homotypic M6-M6 interactions, which was found to be independent of M6 palmitoylation and which might aid in organizing an M6-enriched plasma membrane domain, reminiscent of TEMs. Interestingly, in mammalian cells, palmitoylation of juxtamembrane cysteine residues has been proposed to play an analogous role in targeting angulin-1 to cholesterol-enriched membrane domains at vertices, where angulin-1 recruits tricellulin. However, angulin-1 vertex localization appears to be dispensable for maintaining tricellulin localization after its initial recruitment to TCJs, suggesting that tricellulin is maintained at vertices through association with other factors, for example, with claudin-based TJ strands. Analogously, in Drosophila, M6 palmitoylation is required early during TCJ formation for efficient targeting of M6 and Aka to vertices, whereas Aka is subsequently stabilized at TCJs through interaction with components of SJ limiting strands, including Gli (Esmangart de Bournonville, 2020). Thus, although TCJs of vertebrates and invertebrates comprise different sets of proteins, the current findings suggest that in both cases juxtamembrane palmitoylation contributes to targeting TM proteins to cell vertices during TCJ assembly (Schleutker, 2024).

Attachment and detachment of cortical myosin regulates cell junction exchange during cell rearrangement in the Drosophila wing epithelium

Epithelial cells remodel cell adhesion and change their neighbors to shape a tissue. This cellular rearrangement proceeds in three steps: the shrinkage of a junction, exchange of junctions, and elongation of the newly generated junction. By combining live imaging and physical modeling, this study showed that the formation of myosin-II (myo-II) cables around the cell vertices underlies the exchange of junctions in the Drosophila wing epithelium. The local and transient detachment of myo-II from the cell cortex is regulated by the LIM domain-containing protein Jub and the tricellular septate junction protein M6. Moreover, M6 shifts to the adherens junction plane on jub RNAi and that Jub is persistently retained at reconnecting junctions in m6 RNAi cells. This interplay between Jub and M6 can depend on the junction length and thereby couples the detachment of cortical myo-II cables and the shrinkage/elongation of the junction during cell rearrangement. Furthermore, this study developed a mechanical model based on the wetting theory and clarified how the physical properties of myo-II cables are integrated with the junction geometry to induce the transition between the attached and detached states and support the unidirectionality of cell rearrangement. Collectively, this study elucidates the orchestration of geometry, mechanics, and signaling for exchanging junctions (Ikawa, 2023).

Cell rearrangement plays a fundamental role in shaping a tissue and developing multicellular patterns.Cell rearrangement proceeds in three steps: the shrinkage of a junction, exchange of junctions around the cell vertex (four-way or higher-folded), and elongation of the newly generated junction. The molecular mechanisms underlying junction shrinkage and elongation have been well characterized. At the apical level, medial actomyosin flow and junctional recruitment of myosin-II (myo-II) lead to the generation of forces that shrink and elongate a junction. At the basolateral level, actin-rich protrusions deform the cell membrane. In sharp contrast, little is known regarding how epithelial cells exchange junctions during cell rearrangement (Ikawa, 2023).

Molecules comprising the junctional structure play essential roles in the development of epithelial tissue, where the bicellular junction (bCJ) including the adherence junction (AJ) adheres cells, and the tricellular junction (TCJ) seals the tissue at the cell vertex. During cell rearrangement, as the bCJ dynamically changes its length, the position of the TCJ changes. The junction deformation and vertex displacement are determined by the balance between the constriction force generated by myo-II and the adhesive force generated by cell adhesion molecules such as E-cadherin. The mechanical force balance is tuned by actin-AJ linkers, which are responsible for the linkage between actomyosin and E-cadherin, and TCJ proteins, which are a class of proteins comprising the cell vertex structures, to maintain cell adhesion during the junction shrinkage and control the speed of junction elongation (Ikawa, 2023).

The localization and activity of these molecules need to be coordinated such that cell adhesion is weakened specifically at short junctions around the cell vertex and such that de novo formation of cell adhesion is initiated between the correct pair of cells. The mechanism underlying the coordination of cell adhesion and the regulatory molecules during the junction exchange is unclear (Ikawa, 2023).

Recent studies identified a cytoskeleton structure that could be critical in the junction exchange. It has been shown that myo-II transiently forms rectangle-shaped cables around the cell vertices at the AJ plane in Drosophila wing epithelium (hereafter called rsMCs [rectangle-shaped myo-II cables]). Such local detachment of myo-II from short junctions has been reported in other epithelial tissues.The rsMC may represent a temporally loosened junctional structure, which facilitates the reconnection of junctions. However, the molecular and physical basis of rsMC dynamics and function have not been studied extensively (Ikawa, 2023).

This study sought to identify the mechanism by which apical junctions are exchanged during cell rearrangement in the Drosophila wing epithelium. The findings demonstrate that the precise control of rsMC formation supports the exchange of junctions and the stabilization of newly generated junctions. The rsMC formation is coupled with the junction shrinkage and elongation via an interplay between the LIM domain-containing protein Jub and the TCJ protein M6. A mechanical model based on the wetting theory can explain the junction-length-dependent transition between the detached and attached states of cortical myo-II and the unidirectionality of cell rearrangement. The coupling between junction geometry, mechanics, and signaling identified in the present study may function in other aspects of morphogenesis, as all morphogenetic events are associated with spatio-temporal changes in these three aspects (Ikawa, 2023).

This study delineates the mechanism by which junctions are exchanged in epithelial cells (see Summary and working hypothesis of the mechanism of junction exchange). The size and duration time of the rectangle-shaped myo-II cables (rsMC) are autonomously coordinated through the junction geometry and mechanics to loosen the junctional structure locally and transiently. The transient formation of the rsMC may prevent dilution of DE-cad at loosened junctions as suggested by the decrease of DE-cad signal at long-lasting rsMCs and the observation that jub RNAi resulted in the increase in the gap in junctional DE-cad at 27 h APF. In addition, the directional information of the shrinking junction is inherited by the differential myo-II accumulation along the vertical and horizontal edges of the rsMC, which ensures unidirectional cell rearrangement by inducing the reattachment to junctions along edges with lower myo-II levels. This represents an advantage of the rsMC-mediated mechanism over in situ regulation at cell-cell contact surfaces in supporting the fidelity of junction exchange (Ikawa, 2023).

M6 is not detected in immature epithelial cells, including germband cells, and cells start to express M6 as the epithelium matures. Thus, immature epithelial cells such as germband cells may deform cell membranes via actin-rich basolateral protrusions to form a multicellular rosette. In contrast, mature epithelial cells such as pupal wing cells may reconnect junctions at more apical sides via M6. The mechanism whereby M6 regulates AJ components such as Jub in wing cells and Cno in RasV12-overexpressing eye disc cells remains unclear. Since the mammalian homolog of M6 is involved in the actin regulation, M6 may control actin remodeling, which is known to affect the structure and dynamics of AJ. Alternatively, M6 may directly interact with the AJ components through a rapid, short-term translocation to the AJ, as the position of junction compartments can dynamically change during the development (Ikawa, 2023).

More experiments such as simultaneous tracking of the AJ and SJ components will be necessary to elucidate how AJ and SJ interact and coordinate during junction exchange. A simple theoretical model was introduced, and the mechanical and geometrical conditions were uncovered under which cortical myo-II cables attach to and detach from the junction. These conditions are compatible with the temporal changes in myo-II and jub levels in WT and RNAi cells. However, the model considers only the static force balance and thus cannot describe the entire process of junction exchange. To understand the dynamics of junction exchange, a more comprehensive model, including the turnover of actomyosin and junction components, needs to be developed. Recently, it has been proposed the apposed-cortex adhesion model, which investigates how the duration of cell-cell membrane linkage at the molecular scale affects cell rearrangement (Ikawa, 2023).

Extending the model to incorporate the concept of apposed-cortex adhesion model is an interesting direction for future research (Ikawa, 2023).

In conclusion, the present study shed light on the orchestration of geometry, mechanics, and signaling around the cell vertex for reconnection of junctions. The proposed mechanism can potentially contribute to other aspects of morphogenesis. For instance, the rsMC-like structure at the vertex of a non-remodeling junction implies its relevance in a ratchet-like movement of the vertex along the junction. In addition, because loss of function of M6 causes excess extrusion of cancer cells, it is possible that M6 and actin-AJ linkers function to sense the risk of fracture at cell vertices, thereby preventing the formation of wounds in the epithelium. Given recent findings on the reorganization of the cytoskeleton and information sensing at the cell vertex, further dissecting the complex interplay between actin-AJ regulators, TCJ proteins, and the geometry and mechanics at the vertices will clarify the origin of collective cell behaviors in epithelial development and plasticity (Ikawa, 2023).

The Transmembrane Proteins M6 and Anakonda Cooperate to Initiate Tricellular Junction Assembly in Epithelia of Drosophila

Cell vertices in epithelia comprise specialized tricellular tricellular junctions (TCJs) that seal the paracellular space between three adjoining cells. Although TCJs play fundamental roles in tissue homeostasis, pathogen defense, and in sensing tension and cell shape, how they are assembled, maintained, and remodeled is poorly understood. In Drosophila, the transmembrane proteins Anakonda (Aka) and Gliotactin (Gli) are TCJ components essential for epithelial barrier formation. Additionally, the conserved four-transmembrane-domain protein M6, the only myelin proteolipid protein (PLP) family member in Drosophila, localizes to TCJs. PLPs associate with cholesterol-rich membrane domains and induce filopodia formation and membrane curvature, and Drosophila M6 acts as a tumor suppressor, but its role in TCJ formation remained unknown. This study shows that M6 is essential for the assembly of tricellular, but not bicellular, occluding junctions, and for barrier function in embryonic epithelia. M6 and Aka localize to TCJs in a mutually dependent manner and are jointly required for TCJ localization of Gli, whereas Aka and M6 localize to TCJs independently of Gli. Aka acts instructively and is sufficient to direct M6 to cell vertices in the absence of septate junctions, while M6 is required permissively to maintain Aka at TCJs. Furthermore, M6 and Aka are mutually dependent for their accumulation in a low-mobility pool at TCJs. These findings suggest a hierarchical model for TCJ assembly, where Aka and M6 promote TCJ formation through synergistic interactions that demarcate a distinct plasma membrane microdomain at cell vertices (Wittek, 2020).

Interplay between Anakonda, Gliotactin, and M6 for Tricellular Junction Assembly and Anchoring of Septate Junctions in Drosophila Epithelium<

In epithelia, tricellular junctions (TCJs) serve as pivotal sites for barrier function and integration of both biochemical and mechanical signals. In Drosophila, TCJs are composed of the transmembrane protein Sidekick at the adherens junction (AJ) level, which plays a role in cell-cell contact rearrangement. At the septate junction (SJ) level, TCJs are formed by Gliotactin (Gli), Anakonda (Aka), and the Myelin proteolipid protein (PLP) M6. Despite previous data on TCJ organization, TCJ assembly, composition, and links to adjacent bicellular junctions (BCJs) remain poorly understood. This study has characterized the making of TCJs within the plane of adherens junctions (tricellular adherens junction [tAJ]) and the plane of septate junctions (tricellular septate junction [tSJ]) and reports that their assembly is independent of each other. Aka and M6, whose localizations are interdependent, act upstream to localize Gli. In turn, Gli stabilizes Aka at tSJ. Moreover, tSJ components are not only essential at vertex, as it was found that loss of tSJ integrity induces micron-length bicellular SJ (bSJ) deformations. This phenotype is associated with the disappearance of SJ components at tricellular contacts, indicating that bSJs are no longer connected to tSJs. Reciprocally, SJ components are required to restrict the localization of Aka and Gli at vertex. It is proposed that tSJs function as pillars to anchor bSJs to ensure the maintenance of tissue integrity in Drosophila proliferative epithelia (Esmangart de Bournonville, 2020).

Mutations in the Drosophila tricellular junction protein M6 synergize with Ras(V12) to induce apical cell delamination and invasion

Complications from metastasis are responsible for the majority of cancer-related deaths. Despite the outsized medical impact of metastasis, remarkably little is known about one of the key early steps of metastasis: departure of a tumor cell from its originating tissue. It is well documented that cellular delamination in the basal direction can induce invasive behaviors, but it remains unknown if apical cell delamination can induce migration and invasion in a cancer context. To explore this feature of cancer progression, a genetic screen was performed in Drosophila, and mutations in the protein M6 were found to synergize with oncogenic Ras to drive invasion following apical delamination without crossing a basement membrane. Mechanistically, it was observed that M6-deficient Ras(V12) clones delaminate as a result of alterations in a Canoe-RhoA-myosin II axis that is necessary for both the delamination and invasion phenotypes. To uncover the cellular roles of M6, this study showed that it localizes to tricellular junctions in epithelial tissues where it is necessary for the structural integrity of multicellular contacts. This work provides evidence that apical delamination can precede invasion and highlights the important role that tricellular junction integrity can play in this process (Dunn, 2018).

Cells are known to delaminate from their tissues in both the apical and basal directions during development and in disease conditions. Importantly, cell delamination plays a vital role in cancer progression as it is one way that a cancer cell can escape its originating tissue before spreading to more distant sites. During tumor progression, different models have revealed that cell delamination in the apical direction can lead either to the elimination of the delaminated cells or to the overgrowth of those cells. However, invasive behaviors have not been observed to follow apical delamination but instead have been shown to occur only through basal delamination (Dunn, 2018).

During basal delamination-induced invasion, basement membrane degradation and cell invasion into the underlying tissue can be observed in fixed tissues. On the other hand, if cancer cells leave the tissue by migrating and invading following apical delamination, the invasion would not leave such a histologically visible trail as this invasion could occur without crossing the basement membrane but instead through migration along connected tissues. As such, alternate methods in a suitable system would be needed to recognize if apical delamination is able to induce invasion. Thus, although previous work has documented direct basal delamination and invasion during metastasis in animal models and human patients, it does not preclude the possibility that invasion can be initiated by apical delamination as well. Drosophila cancer models are well suited to address the role of apical delamination in inducing invasive behaviors due to their simple tissue architecture that allows for the easy identification of an apical delamination event, as well as established techniques to image intact living tissues over time to follow the fates of apically delaminated cells. This study documents that cell migration and invasion can be induced via apical delamination through the characterization of a tumor suppressor, M6, in Drosophila (Dunn, 2018).

While bicellular junctions have been well studied for their roles in tissue integrity and signaling, the importance of TCJs has been gradually coming to light in recent years as they have been shown to be key players in ionic barrier formation and maintenance, pathogen spread, and orientation of cell division. This study demonstrates that inactivation of a TCJ protein, M6, disrupts the structural integrity of multicellular contacts and induces apical delamination and invasion of otherwise benign RasV12 tumors in a manner dependent upon a Cno-RhoA-MyoII axis. This study thus provides a causative role for TCJ mutations in driving delamination and invasion in vivo, highlighting the importance of these junctions in tissue integrity and cancer biology (Dunn, 2018).

This study demonstrates a functional link between tricellular junctions and RhoA, which is a known cytoskeletal regulator. This finding adds to recent work that has begun suggesting that TCJs act as centers for cytoskeletal organization. It will be interesting to further learn the mechanisms and consequences of functionally linking RhoA and cytoskeletal components to TCJs. Additionally, RhoA is known to affect a variety of proteins and cellular processes in addition to Sqh. As such, it is highly possible that RhoA is inducing apical delamination and invasion through multiple routes in addition to its effects on sqh. Also, since Cno localizes at the adherens junctions, which are apical to M6, it is plausible that M6 only indirectly affects Cno, and thus RhoA, through alterations in epithelial integrity rather than through direct means (Dunn, 2018).

Finally, invasion of cancer cells into surrounding tissues was previously thought to occur only through direct basal delamination and subsequent invasion. This work shows that apical delamination can also precede migration and invasion to distant tissues. Furthermore, since no basement membrane degradation was observed in invasive RasV12; M6-/- clones, the invasion most likely occurs along connected tissues rather than through an apical delamination to the basal penetration route, but further experiments are needed to confirm this hypothesis. Although mammalian anatomy differs markedly from that of the simple architecture of the Drosophila imaginal discs, it will be interesting to learn if apical delamination, such as is observed in early stage human breast cancer, can also precede invasion in mammalian models. Further investigation into this paradigm of apical delamination-induced invasion could aid in understanding of the mechanisms underlying cancer progression and metastasis (Dunn, 2018).

A role for the membrane protein M6 in the Drosophila visual system

Members of the proteolipid protein family, including the four-transmembrane glycoprotein M6a, are involved in neuronal plasticity in mammals. Previous results demonstrated that M6, the only proteolipid protein expressed in Drosophila, localizes to the cell membrane in follicle cells. M6 loss triggers female sterility, which suggests a role for M6 in follicular cell remodeling. These results were the basis of the present study, which focused on the function and requirements of M6 in the fly nervous system. The present study identified two novel, tissue-regulated M6 isoforms with variable N- and C- termini, and showed that M6 is the functional fly ortholog of Gpm6a. In the adult brain, the protein was localized to several neuropils, such as the optic lobe, the central complex, and the mushroom bodies. Interestingly, although reduced M6 levels triggered a mild rough-eye phenotype, hypomorphic M6 mutants exhibited a defective response to light. Based on its ability to induce filopodium formation it is proposed that M6 is key in cell remodeling processes underlying visual system function. These results bring further insight into the role of M6/M6a in biological processes involving neuronal plasticity and behavior in flies and mammals (Zappia, 2012).

M6 membrane protein plays an essential role in Drosophila oogenesis

We had previously shown that the transmembrane glycoprotein M6a, a member of the proteolipid protein (PLP) family, regulates neurite/filopodium outgrowth, hence, M6a might be involved in neuronal remodeling and differentiation. This work focused on M6, the only PLP family member present in Drosophila, and ortholog to M6a. Unexpectedly, it was found that decreased expression of M6 leads to female sterility. M6 is expressed in the membrane of the follicular epithelium in ovarioles throughout oogenesis. Phenotypes triggered by M6 downregulation in hypomorphic mutants included egg collapse and egg permeability, thus suggesting M6 involvement in eggshell biosynthesis. In addition, RNAi-mediated M6 knockdown targeted specifically to follicle cells induced an arrest of egg chamber development, revealing that M6 is essential in oogenesis. Interestingly, M6-associated phenotypes evidenced abnormal changes of the follicle cell shape and disrupted follicular epithelium in mid- and late-stage egg chambers. Therefore, it is proposed that M6 plays a role in follicular epithelium maintenance involving membrane cell remodeling during oogenesis in Drosophila (Zappia, 2011).

Search PubMed for articles about Drosophila M6

Aparicio, G. I., Leon, A., Gutierrez Fuster, R., Ravenscraft, B., Monje, P. V., Scorticati, C. (2023). Endogenous Glycoprotein GPM6a Is Involved in Neurite Outgrowth in Rat Dorsal Root Ganglion Neurons. Biomolecules, 13(4) PubMed ID: 37189342

Chen, W., Guo, L., Wei, W., Cai, C., Wu. G. 2024. Zdhhc1- and Zdhhc2-mediated Gpm6a palmitoylation is essential for maintenance of mammary stem cell activity. Cell Rep 43(9):114762. PubMed ID: 39321020

Dunn, B. S., Rush, L., Lu, J. Y. and Xu, T. (2018). Mutations in the Drosophila tricellular junction protein M6 synergize with Ras(V12) to induce apical cell delamination and invasion. Proc Natl Acad Sci U S A 115(33): 8358-8363. PubMed ID: 30061406

Esmangart de Bournonville, T. and Le Borgne, R. (2020). Interplay between Anakonda, Gliotactin, and M6 for Tricellular Junction Assembly and Anchoring of Septate Junctions in Drosophila Epithelium. Curr Biol. PubMed ID: 32857971

Gregor, A., Kramer, J. M., van der Voet, M., Schanze, I., Uebe, S., Donders, R., Reis, A., Schenck, A., Zweier, C. (2014). Altered GPM6A/M6 dosage impairs cognition and causes phenotypes responsive to cholesterol in human and Drosophila. Hum Mutat, 35(12):1495-1505 PubMed ID: 25224183

Honda, A., Ito, Y., Takahashi-Niki, K., Matsushita, N., Nozumi, M., Tabata, H., Takeuchi, K., Igarashi, M. (2017). Extracellular Signals Induce Glycoprotein M6a Clustering of Lipid Rafts and Associated Signaling Molecules. J Neurosci, 37(15):4046-4064 PubMed ID: 28275160

Ikawa, K., Ishihara, S., Tamori, Y., Sugimura, K. (2023). Attachment and detachment of cortical myosin regulates cell junction exchange during cell rearrangement in the Drosophila wing epithelium. Curr Biol, 33(2):263-275 e264 PubMed ID: 36543168

Sato, Y., Watanabe, N., Fukushima, N., Mita, S., Hirata, T. (2011). Actin-independent behavior and membrane deformation exhibited by the four-transmembrane protein M6a. PLoS One, 6(12):e26702 PubMed ID: 22162747

Schleutker, R., Luschnig, S. (2024). Palmitoylation of proteolipid protein M6 promotes tricellular junction assembly in epithelia of Drosophila. J. Cell Sci. 137(6): jcs261916. PubMed ID: 38345097

Wittek, A., Hollmann, M., Schleutker, R. and Luschnig, S. (2020). The Transmembrane Proteins M6 and Anakonda Cooperate to Initiate Tricellular Junction Assembly in Epithelia of Drosophila. Curr Biol. PubMed ID: 32857972

Zappia, M. P., Bernabo, G., Billi, S. C., Frasch, A. C., Ceriani, M. F., Brocco, M. A. (2012). A role for the membrane protein M6 in the Drosophila visual system. BMC Neurosci, 13:78 PubMed ID: 22762289

Zappia, M. P., Brocco, M. A., Billi, S. C., Frasch, A. C., Ceriani, M. F. (2011). M6 membrane protein plays an essential role in Drosophila oogenesis. PLoS One, 6(5):e19715 PubMed ID: 21603606

date revised: 12 October 2024

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