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由 TRPML3 与 TRPV5 相互作用形成的新型离子通道。

A novel ion channel formed by interaction of TRPML3 with TRPV5.

机构信息

Department of Otolaryngology-HNS, Stanford University School of Medicine, Palo Alto, California, United States of America.

出版信息

PLoS One. 2013;8(2):e58174. doi: 10.1371/journal.pone.0058174. Epub 2013 Feb 28.

DOI:10.1371/journal.pone.0058174
PMID:23469151
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3585263/
Abstract

TRPML3 and TRPV5 are members of the mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels. Based on sequence similarities of the pore forming regions and on structure-function evidence, we hypothesized that the pore forming domains of TRPML and TRPV5/TRPV6 channels have similarities that indicate possible functional interactions between these TRP channel subfamilies. Here we show that TRPML3 and TRPV5 associate to form a novel heteromeric ion channel. This novel conductance is detectable under conditions that do not activate either TRPML3 or TRPV5. It has pharmacological similarity with TRPML3 and requires functional TRPML3 as well as functional TRPV5. Single channel analyses revealed that TRPML3 and TRPV5 heteromers have different features than the respective homomers, and furthermore, that they occur in potentially distinct stoichiometric configurations. Based on overlapping expression of TRPML3 and TRPV5 in the kidney and the inner ear, we propose that TRPML3 and TRPV5 heteromers could have a biological function in these organs.

摘要

TRPML3 和 TRPV5 是瞬时受体电位 (TRP)阳离子通道的 mucolipin (TRPML)和 TRPV 亚家族的成员。基于孔形成区域的序列相似性和结构-功能证据，我们假设 TRPML 和 TRPV5/TRPV6 通道的孔形成结构域具有相似性，表明这些 TRP 通道亚家族之间可能存在功能相互作用。在这里，我们表明 TRPML3 和 TRPV5 形成一种新型的异源二聚体离子通道。在不激活 TRPML3 或 TRPV5 的情况下，可以检测到这种新型电导。它具有与 TRPML3 相似的药理学特性，并且需要功能性的 TRPML3 和功能性的 TRPV5。单通道分析表明，TRPML3 和 TRPV5 异源二聚体的特征不同于各自的同源二聚体，此外，它们可能以不同的化学计量比存在。基于 TRPML3 和 TRPV5 在肾脏和内耳中的重叠表达，我们提出 TRPML3 和 TRPV5 异源二聚体可能在这些器官中具有生物学功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/2b4cdac3e05b/pone.0058174.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/255104c86627/pone.0058174.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/e334bb7b08c4/pone.0058174.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/4789139193b4/pone.0058174.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/7a3b96d730ce/pone.0058174.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/1ae3d8700005/pone.0058174.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/2b4cdac3e05b/pone.0058174.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/255104c86627/pone.0058174.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/e334bb7b08c4/pone.0058174.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/4789139193b4/pone.0058174.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/7a3b96d730ce/pone.0058174.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/1ae3d8700005/pone.0058174.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af21/3585263/2b4cdac3e05b/pone.0058174.g006.jpg

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