Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons
Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons
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DOI：
10.1038/nn.2873
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发表时间：
2011-08-01
影响因子：
25
通讯作者：
Lewin, Gary R.
中科院分区：
文献类型：
--
作者：
Chiang, Li-Yang;Poole, Kate;Lewin, Gary R.
层粘连蛋白332是真皮-表皮皮肤基底膜的主要成分，维持皮肤的完整性。通过皮肤的感觉末端将机械力转化为电信号需要机械敏感通道。我们发现小鼠表皮角质形成细胞产生一种抑制感觉机械转导的基质，其活性分子成分是层粘连蛋白332。底物结合层粘连蛋白332特异性抑制一种独立于整合素受体激活的机械敏感电流（快速适应）。这种机械转导抑制可以局部发挥作用，并通过阻止电流激活所需的蛋白质系链的形成来介导。我们还发现层粘连蛋白332可以局部控制感觉轴突分支行为。人类层粘连蛋白332的缺失导致感觉末端分支增加，并可能导致机械敏感电流的去抑制。这些先前未知的基质分子的功能可能解释了缺乏层粘连蛋白332的大疱性表皮松解症患者所经历的一些极端疼痛。
Laminin-332 is a major component of the dermo-epidermal skin basement membrane and maintains skin integrity. The transduction of mechanical force into electrical signals by sensory endings in the skin requires mechanosensitive channels. We found that mouse epidermal keratinocytes produce a matrix that is inhibitory for sensory mechanotransduction and that the active molecular component is laminin-332. Substrate-bound laminin-332 specifically suppressed one type of mechanosensitive current ( rapidly adapting) independently of integrin-receptor activation. This mechanotransduction suppression could be exerted locally and was mediated by preventing the formation of protein tethers necessary for current activation. We also found that laminin-332 could locally control sensory axon branching behavior. Loss of laminin-332 in humans led to increased sensory terminal branching and may lead to a de-repression of mechanosensitive currents. These previously unknown functions for this matrix molecule may explain some of the extreme pain experienced by individuals with epidermolysis bullosa who are deficient in laminin-332.