Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
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脊髓性肌萎缩症（SMA，也称为遗传性运动神经病）和遗传性运动和感觉神经病（HMSN）是周围神经系统的临床和遗传异质性疾病。在这里，我们报告TRPV4基因突变导致先天性远端SMA、肩胛骨SMA、HMSN 2C。我们在五个家族中发现了影响 TRPV4 离子通道细胞内 N 端锚蛋白结构域的三个错义取代（R269H、R315W 和 R316C）。突变 TRPV4 构建体在 HeLa 系细胞中的表达揭示了突变蛋白的表面定位减少。此外，即使在用TRPV4通道特异性激动剂4αPDD和低渗溶液刺激后，TRPV4调节的Ca2+流入也显着减少。总之，我们描述了一种由TRPV4突变引起的新的遗传性通道病，并提供证据表明N末端锚蛋白结构域的取代影响通道成熟，导致功能性TRPV4通道的表面表达减少。
Spinal muscular atrophies (SMA, also known as hereditary motor neuropathies) and hereditary motor and sensory neuropathies (HMSN) are clinically and genetically heterogeneous disorders of the peripheral nervous system. Here we report that mutations in the TRPV4 gene cause congenital distal SMA, scapuloperoneal SMA, HMSN 2C. We identified three missense substitutions (R269H, R315W and R316C) affecting the intracellular N-terminal ankyrin domain of the TRPV4 ion channel in five families. Expression of mutant TRPV4 constructs in cells from the HeLa line revealed diminished surface localization of mutant proteins. In addition, TRPV4-regulated Ca2+ influx was substantially reduced even after stimulation with 4αPDD, a TRPV4 channel-specific agonist, and with hypo-osmotic solution. In summary, we describe a new hereditary channelopathy caused by mutations in TRPV4 and present evidence that the resulting substitutions in the N-terminal ankyrin domain affect channel maturation, leading to reduced surface expression of functional TRPV4 channels.
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影响因子：
4.8
作者：
Suzuki, M;Mizuno, A;Imai, M
通讯作者：
Imai, M
影响因子：
4.8
作者：
Erler, Isabell;Al-Ansary, Dalia M. M.;Niemeyer, Barbara A.
通讯作者：
Niemeyer, Barbara A.
DOI：
10.1073/pnas.0606728103
发表时间：
2006-12-12
影响因子：
11.1
作者：
Weissmann, Norbert;Dietrich, Alexander;Gudermann, Thomas
通讯作者：
Gudermann, Thomas
DOI：
10.1073/pnas.1735416100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Liedtke, W;Friedman, JM
通讯作者：
Friedman, JM
影响因子：
64.8
作者：
van Rossum, DB;Patterson, RL;Snyder, SH
通讯作者：
Snyder, SH