Molecular determinants of TRPV4 channel regulation
TRPV4 is a non-selective cation channel with a wide expression and multiple cellular and systemic functions. Described initially as an osmosensor, it can also be activated by temperature and cell swelling. Due to this variety of activating stimuli it may have a promiscuous gating behavior which is m...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2011 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/53592 |
| Acceso en línea: | http://hdl.handle.net/10803/53592 |
| Access Level: | acceso abierto |
| Palabra clave: | TRPV4 Transient receptor potential channel PACSIN3 Hyponatremia Osmoregulation InsP3 receptor Calcium channel Hiponatrèmia Osmoregulació Canal de Calci 577 |
| Sumario: | TRPV4 is a non-selective cation channel with a wide expression and multiple cellular and systemic functions. Described initially as an osmosensor, it can also be activated by temperature and cell swelling. Due to this variety of activating stimuli it may have a promiscuous gating behavior which is mostly unknown. This Thesis research aims to get in-depth in the understanding of the molecular determinants of TRPV4 regulation. I provide evidences that the inositol trisphosphate receptor and its modulatory function on TRPV4 relies on its binding to the C-terminal tail of TRPV4. I discuss the role of the channels’ N-terminal tail in osmotransduction and show how a mutation that results in a channel with an impaired response to osmotic environments is associated to a pathophysiological condition such as hyponatremia. I also highlight the importance of this N-terminal tail and the binding to the regulatory protein PACSIN3 for the global conformation of the channel. |
|---|