Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation.
Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation.
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DOI：
10.3858/emm.2012.44.12.080
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发表时间：
2012-12-31
影响因子：
12.8
通讯作者：
Chun J
中科院分区：
文献类型：
--
作者：
Kang SS;Shin SH;Auh CK;Chun J
瞬时受体电位香草酸4(TRPV4)阳离子通道是色氨酸香草酸亚家族成员之一，广泛表达于多种组织中，参与钙信号的产生和膜电位的去极化。调节细胞表面TRPV4的丰度是渗透和机械转导的关键。TRPV4基因缺陷是几种人类疾病的原因，包括3型短臂畸形(MIM：113500)(也称为臂丛或脊柱干骺端发育不良Kozlowsk型[MIM：118452])和化生发育不良(MIM：156530)(也称为中生性侏儒症或中枢性侏儒症[MIM：168400])。这些骨发育不良突变的特征是严重的侏儒症、脊柱后凸、四肢扭曲和弯曲，以及大关节的收缩。这些疾病的特征是骨密度降低，长骨弯曲，颈椎，软骨内骨化明显不规则，并有钙化斑点和放射状透明骨痂、干骺端和骨顶的条纹。在这篇综述中，我们讨论了突变对TRPV4功能调节的潜在影响，TRPV4功能与人类疾病有关。特别是，我们强调了结构性活性TRPV4突变体如何影响软骨内骨化，肥大的软骨细胞数量减少，以及原发矿化区内软骨岛的存在。此外，我们还总结了目前关于TRPV4在几种疾病发病机制中的作用的知识。
The transient receptor potential vanilloid 4 (TRPV4) cation channel, a member of the TRP vanilloid subfamily, is expressed in a broad range of tissues where it participates in the generation of Ca2+ signals and/or depolarization of the membrane potential. Regulation of TRPV4 abundance at the cell surface is critical for osmo- and mechanotransduction. Defects in TRPV4 are the cause of several human diseases, including brachyolmia type 3 (MIM:113500) (also known as brachyrachia or spondylometaphyseal dysplasia Kozlowski type [MIM:118452]), and metatropic dysplasia (MIM:156530) (also called metatropic dwarfism or parastremmatic dwarfism [MIM:168400]). These bone dysplasia mutants are characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the extremities, and contractures of the large joints. These diseases are characterized by a combination of decreased bone density, bowing of the long bones, platyspondyly, and striking irregularities of endochondral ossification with areas of calcific stippling and streaking in radiolucent epiphyses, metaphyses, and apophyses. In this review, we discuss the potential effect of the mutation on the regulation of TRPV4 functions, which are related to human diseases through deviated function. In particular, we emphasize how the constitutive active TRPV4 mutant affects endochondral ossification with a reduced number of hypertrophic chondrocytes and the presence of cartilage islands within the zone of primary mineralization. In addition, we summarize current knowledge about the role of TRPV4 in the pathogenesis of several diseases.
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影响因子：
2.9
作者：
Inada H;Procko E;Sotomayor M;Gaudet R
通讯作者：
Gaudet R
DOI：
10.1002/ajmg.10269
发表时间：
2002-03-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Amor, DJ;Tudball, C;Savarirayan, R
通讯作者：
Savarirayan, R
影响因子：
4.8
作者：
Fecto, Faisal;Shi, Yong;Deng, Han-Xiang
通讯作者：
Deng, Han-Xiang
DOI：
10.1083/jcb.200409070
发表时间：
2005-03-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Andrade YN;Fernandes J;Vázquez E;Fernández-Fernández JM;Arniges M;Sánchez TM;Villalón M;Valverde MA
通讯作者：
Valverde MA
DOI：
10.1074/jbc.m110.192286
发表时间：
2011-05-27
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Feng S;Rodat-Despoix L;Delmas P;Ong AC
通讯作者：
Ong AC