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brivido-1: Biological Overview | References

How touch is sensed is fundamental for many physiological processes. However, the underlying mechanism and molecular identity for touch sensation are largely unknown. This study reports on defective gentle-touch behavioral responses in brv1 loss-of-function Drosophila larvae. RNAi and Ca(2+) imaging confirmed the involvement of Brv1 in sensing touch and demonstrated that Brv1 mediates the mechanotransduction of class III dendritic arborization neurons. Electrophysiological recordings further revealed that the expression of Brv1 protein in HEK293T cells gives rise to stretch-activated cation channels. Purified Brv1 protein reconstituted into liposomes were found to sense stretch stimuli. In addition, co-expression studies suggested that Brv1 amplifies the response of mechanosensitive ion channel NOMPC (no mechanoreceptor potential C) to touch stimuli. Altogether, these findings demonstrate a molecular entity that mediates the gentle-touch response in Drosophila larvae, providing insights into the molecular mechanisms of touch sensation (Zhang, 2018).

Touch sensation is the ability to sense and respond to mechanical stimuli, and it is essential for fundamental behaviors, including harm avoidance, environmental exploration, and social exchange. The mechanotransduction of touch relies on mechanosensitive ion channels that transform mechanical stimuli into electrical signals in sensory neurons. Genetic dissection of touch transduction in Drosophila larvae has led to the identification of several candidates that may sense mechanical forces. Painless, a TRPA channel subunit expressed in a subset of larval type II multiple dendritic neurons, is involved in mechanical nociception. The DEG/ENaC channel Pickpocket and Drosophila PIEZO (dPIEZO) are essential for noxious mechanosensation in class IV dendritic arborization (da) neurons. The Drosophila TRPN channel NOMPC (no mechanoreceptor potential C) is highly expressed in class III da neurons and is required for gentle-touch sensation (Yan, 2013). Among these channels, dPIEZO and NOMPC have been shown to form mechanically activated channels with distinct biophysical and pore-related properties. Although these findings have advanced knowledge of the physics and physiology of touch sensation, new molecular entities and underlying mechanisms in sensory neurons remain to be identified and characterized to unravel the complexity of touch (Zhang, 2018).

Brv1 is a member of the TRPP (TRP polycystin) subfamily of TRP ion channels and is known for its role in cold sensation in the fly antenna (Gallio, 2011). Brv1 shares sequence homology with the mammalian TRPP2 channels (also known as PKD2). TRPP2 is a Ca2+-permeable cation channel and functions as part of a polycystin receptor-channel complex that senses fluid flow and induces a Ca2+ signal response. These findings suggest a role of TRPP2 in mechanosensation; however, whether Brv1 participates in mechanical responses has remained unclear (Zhang, 2018).

This study reports the role of Drosophila Brv1 in touch sensation. Behavioral assay and Ca2+ responses indicated that Brv1 is required for class III da sensory neurons to sense gentle touch. It was further demonstrated that Brv1 confers stretch-activated currents when heterologously expressed in a mammalian expression system and reconstituted into proteoliposomes. In addition, a co-expression study suggested that Brv1 amplifies the response of NOMPC channels in touch sensation. These findings demonstrate that Brv1 mediates the gentle-touch response in Drosophila larvae (Zhang, 2018).

The foundational observation here is that Brv1, a member of the TRPP subfamily, is required for Drosophila larvae to sense gentle touch. This study electrophysiologically characterized Brv1 as a pore-forming subunit of a cation channel that is activated in response to stretch, suggesting the direct role of Brv1 as a mechanosensitive channel in the touch response. Brv1 is characterized as distinct from other mechanosensitive ion channels, such as NOMPC. NOMPC functioned as a Drosophila touch sensor in response to multiple mechanical forces, including stretching and poking, while Brv1 was insensitive to poking. Touch is a complex sense comprising diverse modalities. A diverse array of specialized mechanoreceptors is involved in detecting a range of mechanical stimuli, including light brush, stretch, vibration, deflection of hair, and pressure. For example, slowly adapting type 2 (SA2) afferents, which innervate Ruffini cylinders, are primarily sensitive to skin stretch (Birznieks, 2009). The kinds of forces experienced during object manipulation activate SA2 stretch-sensitive afferents, which contribute to touch sensation such as grip control. So it may not be a surprise that Brv1 acts as a stretch-sensitive channel to mediate touch sensation. The distinctions in the detection of variable forces may offer the first hints of differences in the activation mechanisms between Brv1 and NOMPC. NOMPC has been suggested to adopt a tether gating mechanism by which the N-terminal ankyrin repeats form a tether linking the channel and the microtubules to convey force (Zhang, 2015). The finding that Brv1 was mechanically gated in the liposome suggests that mechanical force is transmitted directly to the Brv1 channel through lateral membrane tension. However, detailed structural information would be needed to elucidate the gating mechanism of Brv1 in touch sensation (Zhang, 2018).

NOMPC is also recognized as required for gentle-touch sensation in class III neurons (Yan, 2013), which raises the questions of whether Brv1 and NOMPC work together to mediate touch sensation and how they are required for responding to gentle touch. This study found that co-expression of Brv1 and NOMPC in HEK293T cells led to increased amplitude and delayed adaptation of the poke current compared to NOMPC expression alone. Extracellular recordings from class III neurons in abdominal segments of larval fillets has revealed that touching the body wall induces a burst of action potentials, which adapt with a time constant of ~150 ms, but heterologous expression of NOMPC in S2 cells reveals that the poking currents adapt quickly, within 2 ms. Brv1 might act as an amplifier of NOMPC in response to poking, thus enhancing the excitability of class III da neurons in the touch response. A similar mechanism, by which TRPP2 inhibits the stretch-activated ion channels in vascular smooth muscle cells to regulate pressure sensing, has been reported (Sharif-Naeini, 2009). These data suggest double roles of Brv1 in touch sensation: the direct role as a mechanosensitive channel and perhaps the indirect role as a modulator for the NOMPC channel. This may partially explain why Brv1 or NOMPC LOF mutants cause severe defects in the behavioral response; however, the comprehensive role of Brv1 in touch sensation and the underlying molecular mechanisms need to be resolved in the future (Zhang, 2018).

Search PubMed for articles about Drosophila Brivido

Birznieks, I., Macefield, V. G., Westling, G. and Johansson, R. S. (2009). Slowly adapting mechanoreceptors in the borders of the human fingernail encode fingertip forces. J Neurosci 29(29): 9370-9379. PubMed ID: 19625527

Gallio, M., Ofstad, T. A., Macpherson, L. J., Wang, J. W. and Zuker, C. S. (2011). The coding of temperature in the Drosophila brain. Cell 144(4): 614-624. PubMed ID: 21335241

Sharif-Naeini, R., Folgering, J. H., Bichet, D., Duprat, F., Delmas, P., Patel, A. and Honore, E. (2010). Sensing pressure in the cardiovascular system: Gq-coupled mechanoreceptors and TRP channels. J Mol Cell Cardiol 48(1): 83-89. PubMed ID: 19345226

Yan, Z., Zhang, W., He, Y., Gorczyca, D., Xiang, Y., Cheng, L. E., Meltzer, S., Jan, L. Y. and Jan, Y. N. (2013). Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation. Nature 493(7431): 221-225. PubMed ID: 23222543

Zhang, M., Li, X., Zheng, H., Wen, X., Chen, S., Ye, J., Tang, S., Yao, F., Li, Y. and Yan, Z. (2018). Brv1 is required for Drosophila larvae to sense gentle touch. Cell Rep 23(1): 23-31. PubMed ID: 29617663

Zhang, W., Cheng, L.E., Kittelmann, M., Li, J., Petkovic, M., Cheng, T., Jin, P., Guo, Z., Göpfert, M.C., Jan, L.Y. and Jan, Y.N. (2015). Ankyrin repeats convey force to gate the NOMPC mechanotransduction channel. Cell 162: 1391-1403. PubMed ID: 26359990

date revised: 23 September 2018

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