InteractiveFly: GeneBrief

Nucleoporin 44A: Biological Overview | References

The nuclear pore complex (NPC) mediates the transport of macromolecules between the nucleus and cytoplasm. Recent evidence indicates that structural nucleoporins, the building blocks of the NPC, have a variety of unanticipated cellular functions. This study reports an unexpected tissue-specific requirement for the structural nucleoporin Seh1 during Drosophila oogenesis. Seh1 is a component of the Nup107-160 complex, the major structural subcomplex of the NPC. Seh1 associates with the product of the missing oocyte (mio) gene. In Drosophila, mio regulates nuclear architecture and meiotic progression in early ovarian cysts. Like mio, seh1 has a crucial germline function during oogenesis. In both mio and seh1 mutant ovaries, a fraction of oocytes fail to maintain the meiotic cycle and develop as pseudo-nurse cells. Moreover, the accumulation of Mio protein is greatly diminished in the seh1 mutant background. Surprisingly, characterization of a seh1 null allele indicates that, although required in the female germline, seh1 is dispensable for the development of somatic tissues. This work represents the first examination of seh1 function within the context of a multicellular organism. Seh1 has been shown to play a role in the construction and/or maintenance of bipolar spindles in multiple organisms. In summary, these studies demonstrate that Mio is a novel interacting partner of the conserved nucleoporin Seh1 and add to the growing body of evidence that structural nucleoporins can have novel tissue-specific roles (Senger, 2011).

The pathways that control progression through the early meiotic cycle remain poorly understood in metazoans. Drosophila melanogaster provides a genetically tractable system with which to study the relationship between early meiotic progression and oocyte development. As in mammals and Xenopus, the Drosophila oocyte initiates meiosis within the context of a germline cyst. Drosophila ovarian cysts are produced through a series of four synchronous mitotic divisions during which cytokinesis is incomplete. Soon after the completion of the mitotic divisions, all 16 cells enter premeiotic S phase. However, only the true oocyte, which comprises one of the two cells at the center of the syncytium, remains in meiosis and goes on to produce a gamete. The other 15 cells lose their meiotic features, enter the endocycle, and develop as polyploid nurse cells. In contrast to the nurse cells, the single oocyte remains in prophase of meiosis I until it proceeds to the first meiotic metaphase late in oogenesis. The pathways that drive this complicated series of cell cycle transitions that are so critical to the development of the mature gamete remain a topic of great interest (Senger, 2011).

The missing oocyte (mio) gene was identified in a forward genetic screen for mutants affecting cell cycle regulation and oocyte differentiation in early ovarian cysts (Iida, 2004). In mio mutants, the oocyte enters the meiotic cycle, forms mature synaptonemal complexes and accumulates oocyte-specific markers. However, in the absence of Mio, the oocyte fate is not stably maintained. Soon after the nurse cells enter the endocycle in stage 1 of oogenesis, mio oocytes follow the nurse cells into the endocycle, lose the preferential accumulation of oocyte-specific markers and develop as pseudo-nurse cells. Thus, mio is required for the maintenance of the meiotic cycle and oocyte identity. The mio gene encodes a 975 amino acid protein that is highly conserved from yeast to humans (Iida, 2004). Yet, the molecular function of mio remains elusive. This study demonstrates that Mio associates with the conserved nucleoporin Seh1 (also known as Nup44A in Drosophila). Moreover, this study define a tissue-specific requirement for Seh1 during oogenesis (Senger, 2011).

Seh1 is a component of a nucleoporin subcomplex known as the Nup107-160 complex in higher eukaryotes and the Nup84 complex in yeast (Fahrenkrog, 2004; Hetzer, 2005; Wozniak, 2010). The Nup107-160 complex, which is the major structural component of the nuclear pore complex (NPC), consists of at least nine subunits in higher eukaryotes and functions in the regulation of mRNA export as well as in the assembly and distribution of NPCs within the nuclear envelope (Hetzer, 2005; Wozniak, 2010). Studies over the last five years have defined several physiological functions for the Nup107-160/Nup84 complex that appear to be independent of nucleocytoplasmic transport (Fahrenkrog, 2004; Wozniak, 2010). Most notably, in Xenopus egg extracts and HeLa cells, the Nup107-160 complex has a dynamic localization during the cell cycle (Hetzer, 2005). Although present on the nuclear envelope in interphase, the entire complex targets to kinetochores, spindles and spindle poles to varying extents during mitosis (Loiodice, 2004; Orjalo, 2006). Consistent with a mitotic function, depleting components of the Nup107-160 complex results in cell cycle abnormalities, including defects in mitotic spindle formation, chromosome segregation and cytokinesis (Orjalo, 2006; Platani, 2009). Moreover, recent evidence indicates that in HeLa cells and Xenopus egg extracts, the Nup107-160 complex mediates microtubule nucleation at kinetochores via its interaction with the γ-TuRC complex (Mishra, 2010). Unlike in other metazoans, in Drosophila Nup107 fails to localize to kinetochores at mitosis but is found concentrated in the spindle region (Katsani, 2008). In summary, the Nup107-160 complex is multifunctional, with roles in both nucleocytoplasmic transport and cell cycle regulation (Senger, 2011).

This study demonstrates that Mio, a protein that is required for maintenance of the meiotic cycle and oocyte fate during oogenesis, associates with the structural nucleoporin Seh1. Surprisingly, it was found that a seh1 deletion allele is viable but exhibits dramatically reduced female fertility. Closer examination reveals that, as is observed in mio mutants, in a fraction of seh1 ovarian cysts oocytes fail to maintain the meiotic cycle and oocyte fate into later stages of oogenesis. From these studies it is concluded that Seh1 has an essential germline function during oogenesis but is not required for the growth or development of somatic tissues (Senger, 2011).

To better understand how Mio influences the maintenance of the meiotic cycle and oocyte fate in Drosophila, proteins that co-purify with Mio were identified by tandem affinity purification. From these experiments, it was determined that Mio is present in a stable complex with the structural nucleoporin Seh1. Seh1 is a component of the Nup107 complex, which is the primary structural unit of the nuclear pore. Studies in multiple organisms indicate that, although Seh1 is a nucleoporin, it is not required for bulk nucleocytoplasmic transport and has a limited role in the localization of other nucleoporins to the NPC (Loiodice, 2004; Orjalo, 2006). In contrast to its limited role at the NPC during interphase, recent evidence indicates that Seh1 has an essential function during mitosis. In Xenopus egg extracts and mammalian tissue culture cells, a fraction of the Nup107 complex that includes Seh1 targets to kinetochores, spindles and/or spindle poles from early prometaphase through early anaphase (Belgareh, 2001; Orjalo, 2006). Moreover, reducing the levels of Nup107-160 components disrupts spindle assembly and cytokinesis (Aitchison, 1995; Bai, 2004; Mishra, 2010; Orjalo, 2006; Platani, 2009; Zuccolo, 2007). Importantly, the specific depletion of seh1 results in the failure of the Nup107 complex to target to kinetochores at mitosis and results in multiple mitotic defects (Zuccolo, 2007; Platani, 2009). Thus, Seh1 plays a role in the construction and/or maintenance of bipolar spindles in multiple organisms (Senger, 2011).

To define the role of Seh1 in Drosophila a seh1^null deletion allele was generated. Considering the key role of Seh1 during mitosis in other organisms, it was surprising to find that seh1^null homozygotes are viable. From this observation it is concluded that seh1 is dispensable in Drosophila for the mitotic cycle during the majority of somatic divisions. Consistent with a limited role for Seh1 during the mitotic cycle, the specific accumulation of Seh1 on kinetochores during mitosis was not observed. Although this might reflect a limitation of the reagents, these data are in agreement with previous work (Katsani, 2008) demonstrating that the core component of the Nup107-160 complex, the nucleoporin Nup107, fails to accumulate at kinetochores during mitosis in multiple Drosophila tissues (Senger, 2011).

These studies also suggest a limited and/or redundant role for Seh1 in supporting the general structure and/or function of the NPC in interphase cells. Specifically, it was found that multiple nucleoporins, including Nup107, target to the NPC in the absence of Seh1 in both germline and somatic tissues. The only nucleoporin mislocalization observed in seh1^null mutants involved a limited displacement of Mtor from the nuclear envelope to the nucleoplasm in meiotic cysts in the germarium. Mtor is a component of the nuclear basket and is present on the cytoplasmic face of the NPC during interphase but relocates to the spindle matrix during mitosis (Lince-Faria, 2009; Qi, 2004). Whether the partial displacement of Mtor in the seh1 background reflects a direct role for Seh1 in recruiting and/or stabilizing Mtor at the NPC remains to be determined (Senger, 2011).

Although dispensable for somatic development, it was found that seh1 has an essential function in the female germline during oogenesis. seh1^null females are nearly sterile, producing only a small number of adult progeny. Indeed, seh1^null females lay fewer eggs and contain ovarioles with a diminished number of egg chambers relative to wild-type females. A possible contributory factor to this reduced egg production is the mitotic delay observed during the ovarian cyst divisions. It was found that in ovaries from seh1 females, stem cells and ovarian cysts in R1 of the germarium spend a greater proportion of their time in mitosis than those in wild-type females. This phenotype is consistent with the metaphase delay observed in mammalian cells and Xenopus egg extracts depleted of members of the Nup107-160 complex, including Seh1. Thus, mutations in seh1 alter the rate of egg chamber production, as well as the nature of the ovarian cyst divisions in the germarium (Senger, 2011).

In addition to affecting the overall rate of egg production, Seh1 influences the differentiation of the oocyte within the ovarian cyst. Similar to what is observed in mio mutants, in a fraction of seh1 ovarian cysts the oocyte enters the endocycle and develops as a pseudo-nurse cell. This does not reflect an inability ofseh1^null oocytes to enter the meiotic cycle. On the contrary, seh1^null ovarian cysts enter the meiotic cycle on schedule with the two pro-oocytes progressing to pachytene, as measured by the construction of a mature synaptonemal complex. However, soon after exiting the germarium, a fraction of seh1 mutant oocytes enter the endocycle and become polyploid. In Drosophila, oocyte differentiation, as well as the maintenance of the meiotic cycle, are contingent on the microtubule-based transport of mRNAs and proteins from the nurse cells to the oocyte (Huynh, 2004). The germline-specific RNA-binding protein Orb starts to accumulate in the oocyte in late R2a of the germarium. Defects that impair the microtubule-dependent accumulation of Orb in the oocyte correlate with the inability to maintain the meiotic cycle through later stages of oogenesis. This study found that in seh1 ovarian cysts, the specific accumulation of Orb in the oocyte, as well as the secondary migration of Orb protein from the anterior to the posterior of the oocyte, are often delayed and/or otherwise defective. Additionally, the microtubule-dependent translocation of centrioles from the anterior to the posterior of the oocyte nucleus in the stage 1 oocyte is defective in both mio and seh1 ovarian cysts. Thus, as is observed with mio, seh1 influences the ability of the oocyte to maintain the meiotic cycle and oocyte fate beyond the germarium (Senger, 2011).

As Seh1 has been implicated in a variety of cellular functions, there are several possibilities as to how it might influence oocyte development and meiotic progression. First, Seh1 might act at the NPC to regulate the nucleocytoplasmic transport of specific molecules required for oocyte differentiation and growth. Second, Seh1 might regulate the activity of Mtor and/or other nucleoporins that have recently been implicated in transcriptional regulation (Vaquerizas, 2010). Finally, consistent with the alterations in mitotic cyst division and Orb localization, Seh1 might directly influence the organization and/or function of microtubules within ovarian cysts. Currently, the third model is favored because it is the most congruent with previous observations on the role of Seh1 in other organisms as well as with the current data (Senger, 2011).

This study has shown that Mio and Seh1 are present in a stable complex and that both proteins are dispensable for somatic development but are required for the development of the mature egg. Additionally, it was found that Seh1 is required for Mio protein stability. In the seh1 mutant background, Mio protein levels are reduced dramatically. Furthermore, depleting seh1 via RNAi in S2 tissue culture cells results in a rapid reduction in Mio protein levels. These results suggest the following simple model. Seh1 influences oocyte growth and the maintenance of the oocyte fate through its ability to promote the stability of the Mio protein. In the absence of Seh1, Mio protein levels fall, resulting in a mio-like phenotype. However, two lines of evidence suggest that Mio and Seh1 have a more complex interaction. First, overexpressing mio in the seh1 mutant background fails to rescue the seh1 phenotype. This failure to rescue is observed even though the seh1 ¹⁵; UAS-mio ovaries have high levels of Mio protein in the germline. This strongly suggests that the seh1 ovarian phenotype is not due solely to the instability of the Mio protein in the absence of Seh1. Second, seh1 acts as a strong dominant suppressor of the mio 16-nurse-cell phenotype. A possible model to explain this counterintuitive result is that mio and seh1 act in opposing directions to regulate a common pathway that is crucial for the maintenance of the oocyte fate. Misregulation of this common pathway by either mio or seh1 could result in the reversion of the oocyte to the default state of nurse cell (Senger, 2011).

In the future, studies of Mio and Seh1 will help elucidate the pathways that drive oocyte development and meiotic progression and contribute to understanding of how individual NPC components drive tissue-specific differentiation (Senger, 2011).

TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila

In single-cell eukaryotes the pathways that monitor nutrient availability are central to initiating the meiotic program and gametogenesis. In Saccharomyces cerevisiae an essential step in the transition to the meiotic cycle is the down-regulation of the nutrient-sensitive target of rapamycin complex 1 (TORC1; see Drosophila Tor pathway) by the increased minichromosome loss 1/ GTPase-activating proteins toward Rags 1 (Iml1/GATOR1) complex in response to amino acid starvation. How metabolic inputs influence early meiotic progression and gametogenesis remains poorly understood in metazoans. This study defined opposing functions for the TORC1 regulatory complexes Iml1/GATOR1 and GATOR2 during Drosophila oogenesis. As is observed in yeast, the Iml1/GATOR1 complex inhibits TORC1 activity to slow cellular metabolism and drive the mitotic/meiotic transition in developing ovarian cysts. In iml1 germline depletions, ovarian cysts undergo an extra mitotic division before meiotic entry. The TORC1 inhibitor rapamycin can suppress this extra mitotic division. Thus, high TORC1 activity delays the mitotic/meiotic transition. Conversely, mutations in Tor, which encodes the catalytic subunit of the TORC1 complex, result in premature meiotic entry. Later in oogenesis, the GATOR2 components Missing oocyte (Mio) and Seh1 are required to oppose Iml1/GATOR1 activity to prevent the constitutive inhibition of TORC1 and a block to oocyte growth and development. These studies represent the first examination of the regulatory relationship between the Iml1/GATOR1 and GATOR2 complexes within the context of a multicellular organism. The data imply that the central role of the Iml1/GATOR1 complex in the regulation of TORC1 activity in the early meiotic cycle has been conserved from single cell to multicellular organisms (Wei, 2014b).

In yeast, the inhibition of the nutrient-sensitive target of rapamycin complex 1 (TORC1) in response to amino acid limitation is essential for cells to transit from the mitotic cycle to the meiotic cycle. In response to amino acid starvation, the Iml1 complex, comprising the Iml1, Nitrogen permease regulator-like 2 (Npr2), and Nitrogen permease regulator-like 3 (Npr3) proteins in yeast and the respective orthologs DEPDC5, Nprl2, and Nprl3 in mammals, inhibits TORC1 activity. The Iml1 complex, which has been renamed the 'GTPase-activating proteins toward Rags 1' (GATOR1) complex in higher eukaryotes, functions as a GTPase-activating protein complex that inactivates RagsA/B or Gtr1 in mammals and yeast, respectively, thus preventing the activation of TORC1. In the yeast Saccharomyces cerevisiae, mutations in the Iml1 complex components Npr2 and Npr3 result in a failure to down-regulate TORC1 activity in response to amino acid starvation and block meiosis and sporulation. As is observed in yeast, in Drosophila, Nprl2 and Nprl3 mediate a critical response to amino acid starvation (Wei, 2014a). However, their roles in meiosis and gametogenesis remain unexplored (Wei, 2014b).

Recent reports indicate that the Iml1, Npr2, and Npr3 proteins are components of a large multiprotein complex originally named the 'Seh1-associated' (SEA) complex in budding yeast and the 'GATOR' complex in higher eukaryotes. The SEA/GATOR complex contains eight highly conserved proteins. The three proteins described above, Iml1/DEPDC5, Npr2/Nprl2, and Npr3/Nprl3, form the Iml1/GATOR1 complex and inhibit TORC1. The five remaining proteins in the complex, Seh1, Sec13, Sea4/Mio, Sea2/WDR24, and Sea3/WDR59, which have been designated the 'GATOR2' complex in multicellular organisms, oppose the activity of Iml1/GATOR1 and thus promote TORC1 activity (Wei, 2014b).

Little is known about the physiological and/or developmental requirements for the GATOR2 complex in multicellular organisms. However, in Drosophila the GATOR2 components Mio and Seh1 interact physically and genetically and exhibit strikingly similar ovarian phenotypes, with null mutations in both genes resulting in female sterility (Senger, 2011; Wei, 2014a). In Drosophila females, oocyte development takes place within the context of an interconnected germline syncytium, also referred to as an 'ovarian cyst'. Ovarian cyst formation begins at the tip of the germarium when a cystoblast, the daughter of a germline stem cell, undergoes four synchronous divisions with incomplete cytokinesis to produce 16 interconnected cells. Actin-stabilized cleavage furrows, called 'ring canals', connect cells within the cyst. Each 16-cell cyst develops with a single oocyte and 15 polyploid nurse cells which ultimately are encapsulated by a somatically derived layer of follicle cells to produce an egg chamber. Each ovary is comprised of ∼15 ovarioles that consist of a single germarium followed by a string of egg chambers in successively older stages of development. In mio- and seh1-mutant egg chambers, the oocyte enters the meiotic cycle, but as oogenesis proceeds, the oocyte fate and the meiotic cycle are not maintained stably (Senger, 2011; Wei, 2014a). Ultimately, a large fraction of mio and seh1 oocytes enter the endocycle and develop as polyploid nurse cells. A mechanistic understanding of how mio and seh1 influence meiotic progression and oocyte fate has remained elusive (Wei, 2014b).

This study demonstrates that the Iml1/GATOR1 complex down-regulates TORC1 activity to promote the mitotic/meiotic transition in Drosophila ovarian cysts. Depleting iml1 in the female germ line delays the mitotic/meiotic transition, so that ovarian cysts undergo an extra mitotic division. Conversely, mutations in Tor result in premature meiotic entry before the completion of the four mitotic divisions. Moreover, it was demonstrated that in the female germ line, the GATOR2 components Mio and Seh1 are required to oppose the TORC1 inhibitory activity of the Iml1/GATOR1 complex to prevent the constitutive down-regulation of TORC1 activity in later stages of oogenesis. These studies represent the first examination of the regulatory relationship between Iml1/GATOR1 and GATOR2 components within the context of a multicellular animal. Finally, these data reveal a surprising tissue-specific requirement for the GATOR2 complex in multicellular organisms and suggest a conserved role for the SEA/GATOR complex in the regulation of TORC1 activity during gametogenesis (Wei, 2014b).

Previous work demonstrated that in Drosophila the Iml1/GATOR1 complex mediates an adaptive response to amino acid starvation. This study tested the hypothesis that the Iml1/GATOR1 complex also has retained a role in the regulation of the early events of gametogenesis. Consistent with this model, this study found that in germline knockdowns of iml1, ovarian cysts delay meiotic entry and undergo a fifth mitotic division. This meiotic delay can be suppressed with the TORC1 inhibitor rapamycin. Thus, during Drosophila oogenesis the Iml1/GATOR1 complex promotes the transition from the mitotic cycle to the meiotic cycle through the down-regulation of the metabolic regulator TORC1. Increasing TORC1 activity by disabling its inhibitor delays meiotic progression, whereas germline clones of a Tor-null allele enter meiosis prematurely. Taken together, these data indicate that the level of TORC1 activity contributes to the timing of the mitotic/meiotic switch in Drosophila females and suggest that low TORC1 activity may be a conserved feature of early meiosis in many eukaryotes (Wei, 2014b).

However, in Drosophila, meiotic entry is not contingent on amino acid limitation at the organismal level. Indeed, the energy-intensive process of Drosophila oogenesis is curtailed dramatically when females do not have access to a protein source. Thus, to promote meiotic entry, Drosophila females must activate the Iml1/GATOR1 complex in a tissue-specific manner, using a mechanism that is independent of the overall nutrient status of the animal. At least two models can explain how Drosophila females might activate the Iml1/GATOR1 complex specifically in the germ line. In the first model, ovarian cysts locally experience low levels of amino acids during the mitotic cyst divisions and/or at the point of meiotic entry. These low levels of amino acids could reflect a non–cell-autonomous effect: The somatically derived escort cells that surround dividing ovarian cysts may function to create a low amino acid environment that triggers the activation of the Iml1/GATOR1 complex within developing ovarian cysts. Alternatively, the effect may be cell autonomous: The germ cells within dividing ovarian cysts may have a reduced ability to sense and/or import amino acids. In a second model, a developmental signaling pathway that is completely independent of local or whole-animal amino acid status directly activates the Iml1/GATOR1 complex. The identification of the upstream requirements for Iml1/GATOR1 activation in the female germ line will help distinguish between these two models (Wei, 2014b).

Although low TORC1 activity is required during early ovarian cyst development to promote the mitotic/meiotic switch, the dramatic growth of egg chambers later in oogenesis is a metabolically expensive process that is predicted to require high TORC1 activity. The current data indicate that the GATOR2 components Mio and Seh1 function to oppose the TORC1-inhibitory activity of the GATOR1 complex in the female germ line. In mio and seh1 mutants, TORC1 activity is constitutively repressed in the germ line of developing egg chambers, resulting in the activation of catabolic metabolism and the blocking of meiotic progression and oocyte development and growth (Wei, 2014b).

Previous data indicate that Mio and Seh1 act very early in oogenesis soon after the formation of the 16-cell cyst. The mio and seh1 ovarian phenotypes can be rescued by depleting the GATOR1 components nprl2, nprl3, or iml1 in the female germ line or by raising baseline levels of TORC1 activity by disabling an alternative TORC1 inhibitory complex, TSC1/2. These data are consistent with the model that the failure to maintain the meiotic cycle and the oocyte fate in mio and seh1 mutants is a direct result of inappropriately low TORC1 activity in the female germ line brought on by the deregulation of the Iml1/GATOR1 complex (Wei, 2014b).

Notably, null alleles of both mio and seh1 are viable, with many somatic tissues exhibiting no apparent developmental abnormalities and only limited reductions in cell growth. Thus, although Mio and Seh1 are critical for the activation of TORC1 and the development of the female gamete, these proteins play a relatively small role in the development and growth of many somatic tissues under nutrient-replete conditions. Whether this small role reflects the fact that components of the Iml1/GATOR1 complex are expressed at low levels in some somatic cell types or that the complex is present but needs to be activated by a signal, such as nutrient stress or a developmental signaling pathway, remains to be elucidated (Wei, 2014b).

In the future it will be important to gain a fuller understanding of the potential environmental and developmental inputs that regulate the activity of the Iml1/GATOR1 and GATOR2 complexes in multicellular organisms. These studies will provide much-needed insight into the basic mechanisms by which both environmental and developmental signaling pathways interface with the metabolic machinery to influence cell growth and differentiation (Wei, 2014b).

Search PubMed for articles about Drosophila Seh1

Aitchison, J. D., Blobel, G., and Rout M. P. (1995). Nup120p: a yeast nucleoporin required for NPC distribution and mRNA transport. J. Cell Biol. 131: 1659-1675. PubMed ID: 8557736

Bai, S. W., et al. (2004). The fission yeast Nup107-120 complex functionally interacts with the small GTPase Ran/Spi1 and is required for mRNA export, nuclear pore distribution, and proper cell division. Mol. Cell. Biol. 24: 6379-6392. PubMed ID: 15226438

Belgareh, N., et al. (2001). An evolutionarily conserved NPC subcomplex, which redistributes in part to kinetochores in mammalian cells. J. Cell Biol. 154: 1147-1160. PubMed ID: 11564755

Fahrenkrog, B., Koser, J. and Aebi, U. (2004). The nuclear pore complex: a jack of all trades? Trends Biochem. Sci. 29: 175-182. PubMed ID: 15082311

Hetzer, M. W., Walther, T. C. and Mattaj, I. W. (2005). Pushing the envelope: structure, function, and dynamics of the nuclear periphery. Annu. Rev. Cell Dev. Biol. 21: 347-380. PubMed ID: 16212499

Iida, T. and Lilly, M. A. (2004). missing oocyte encodes a highly conserved nuclear protein required for the maintenance of the meiotic cycle and oocyte identity in Drosophila. Development 131: 1029-1039. PubMed ID: 14973288

Katsani, K. R., Karess, R. E., Dostatni, N. and Doye V. (2008). In vivo dynamics of Drosophila nuclear envelope components. Mol. Biol. Cell 19: 3652-3666. PubMed ID: 18562695

Lince-Faria, M., et al. (2009). Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator. J. Cell Biol. 184: 647-657. PubMed ID: 19273613

Loiodice, I., et al. (2004). The entire Nup107-160 complex, including three new members, is targeted as one entity to kinetochores in mitosis. Mol. Biol. Cell 15: 3333-3344. PubMed ID: 15146057

Mishra, R. K., et al. (2010). The Nup107-160 complex and gamma-TuRC regulate microtubule polymerization at kinetochores. Nat. Cell Biol. 12: 164-169. PubMed ID: 20081840

Orjalo, A. V., et al. (2006). The Nup107-160 nucleoporin complex is required for correct bipolar spindle assembly. Mol. Biol. Cell 17: 3806-3818. PubMed ID: 16807356

Platani, M., et al. (2009). The Nup107-160 nucleoporin complex promotes mitotic events via control of the localization state of the chromosome passenger complex. Mol. Biol. Cell 20, 5260-5275. PubMed ID: 16807356

Qi, H., et al. (2004). Megator, an essential coiled-coil protein that localizes to the putative spindle matrix during mitosis in Drosophila. Mol. Biol. Cell 15: 4854-4865. PubMed ID: 15356261

Senger, S., Csokmay, J., Akbar, T., Jones, T. I., Sengupta, P. and Lilly, M. A. (2011).The nucleoporin Seh1 forms a complex with Mio and serves an essential tissue-specific function in Drosophila oogenesis. Development 138(10): 2133-42. PubMed ID: 21521741

Vaquerizas, J. M., et al. (2010). Nuclear pore proteins nup153 and megator define transcriptionally active regions in the Drosophila genome. PLoS Genet. 6: e1000846. PubMed ID: 20174442

Wei, Y. and Lilly, M. A. (2014a). The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. Cell Death Differ 21: 1460-1468. PubMed ID: 24786828

Wei, Y., Reveal, B., Reich, J., Laursen, W. J., Senger, S., Akbar, T., Iida-Jones, T., Cai, W., Jarnik, M. and Lilly, M. A. (2014b). TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila. Proc Natl Acad Sci U S A 111(52):E5670-7. PubMed ID: 25512509

Wozniak, R., Burke, B. and Doye, V. (2010). Nuclear transport and the mitotic apparatus: an evolving relationship. Cell. Mol. Life Sci. 67: 2215-2230. PubMed ID: 20372967

Zuccolo, M., et al. (2007). The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions. EMBO J. 26: 1853-1864. PubMed ID: 17363900

date revised: 15 April 2020

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