Unsworth Harriet C, Aasen Trond, McElwaine Suzanne, Kelsell David P
Centre for Cutaneous Research, Queen Mary's School of Medicine and Dentistry, University of London, Whitechapel, E1 4AT, UK.
Hum Mol Genet. 2007 Jan 15;16(2):165-72. doi: 10.1093/hmg/ddl452. Epub 2006 Dec 1.
Channels formed by connexins (Cx), the major protein subunits of gap junctions, allow passage of ions and molecular messengers between cells to provide a mechanism of synchronized cellular response. Twenty human Cx isoforms have been identified and mutations in the gene GJB3 encoding the 31 kDa isoform, Cx31, can cause dominant or recessive skin disease, dominant or recessive deafness or dominant neuropathy with deafness. Cx31 is expressed in differentiating keratinocytes in skin. Here, we also demonstrate endogenous Cx31 expression in human neuronal cell lines, particularly in differentiated neurones. Exogenous Cx31 expression induced neurite outgrowth in human neuronal cell lines, but not differentiation in primary human keratinocytes. Though neither the neuropathy and hearing loss mutation (66delD)Cx31 nor the skin disease associated mutation (R42P)Cx31 is able to traffic to the plasma membrane, the R42P mutant induced neurite outgrowth to a level equal to wild-type Cx31. In contrast, there was significantly reduced neurite outgrowth after (66delD)Cx31 expression. In addition to indicating a potential disease mechanism for the neuropathy/deafness mutation, this work demonstrates a tissue-specific function for Cx31.
连接蛋白（Cx）是间隙连接的主要蛋白质亚基，由其形成的通道允许离子和分子信使在细胞间通过，从而提供一种细胞同步反应的机制。已鉴定出20种人类Cx亚型，编码31 kDa亚型Cx31的基因GJB3发生突变可导致显性或隐性皮肤病、显性或隐性耳聋或伴有耳聋的显性神经病变。Cx31在皮肤中分化的角质形成细胞中表达。在此，我们还证明了人类神经元细胞系中内源性Cx31的表达，尤其是在分化的神经元中。外源性Cx31的表达可诱导人类神经元细胞系中的神经突生长，但不会诱导原代人类角质形成细胞分化。尽管神经病变和听力损失突变体（66delD）Cx31以及与皮肤病相关的突变体（R42P）Cx31均无法转运至质膜，但R42P突变体诱导的神经突生长水平与野生型Cx31相当。相比之下，（66delD）Cx31表达后神经突生长显著减少。除了揭示神经病变/耳聋突变的潜在疾病机制外，这项研究还证明了Cx31具有组织特异性功能。
