Short window of opportunity for calpain induced growth cone formation after axotomy of Aplysia neurons
Short window of opportunity for calpain induced growth cone formation after axotomy of Aplysia neurons
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DOI：
10.1002/neu.10084
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发表时间：
2002-09-15
期刊：
影响因子：
--
通讯作者：
Spira, ME
中科院分区：
文献类型：
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作者：
Gitler, D;Spira, ME
我们的实验室已经确定，通过短暂升高细胞内游离钙离子浓度来局部激活钙蛋白酶对于诱导培养的失智症神经元中生长锥（GC）的形成至关重要。钙蛋白酶参与GC形成的机制和阶段尚不清楚。我们开始研究这些问题，通过确定钙蛋白酶的作用的性质和钙蛋白酶活性影响导致GC形成及其延伸的级联事件的阶段。我们报告说，钙蛋白酶依赖性转化的轴突段成GC发生在一个狭窄的窗口的机会，持续约5分钟。如果钙蛋白酶在此窗口的机会，GC的形成被抑制不会发生。钙蛋白酶的抑制后的机会窗口减慢的速度lamellipodial扩展，但不逮捕it.The血影蛋白，钙蛋白酶底物和膜骨架的主要组成部分，发生在这个窗口的机会，在协议的假设，血影蛋白的蛋白水解是在GC形成的早期步骤。如果蛋白水解的开始被推迟，血影蛋白保持不变，GC的形成受到损害。我们认为钙蛋白酶参与两个不同的过程：它是关键的触发GC的形成，并在GC的板状伪足的扩展过程中起着调节作用。(C)2002 Wiley Periodicals，Inc.
Our laboratory has established that local activation of calpain by a transient elevation of the free intracellular calcium concentration is crucial for the induction of growth cone (GC) formation in cultured Aplysia neurons. The mechanisms and stages in which calpain is involved in the formation of a GC are not known. We began to study these questions by determining the nature of calpain's action and the stages in which calpain activity affects the cascade of events that leads to the formation of the GC and its extension. We report that the calpain-dependent transformation of an axonal segment into a GC occurs within a narrow window of opportunity that lasts approximately 5 min. If calpain is inhibited during this window of opportunity, GC formation does not occur. Inhibition of calpain after the window of opportunity slows down the rate of lamellipodial extension but doesn't arrest it. The proteolysis of spectrin, a calpain substrate and a major component of the membrane skeleton, occurs within this window of opportunity, in agreement with the hypothesis that spectrin proteolysis is an early step in the formation of the GC. If the onset of proteolysis is deferred, spectrin remains unchanged and GC formation is compromised. We suggest that calpain participates in two different processes: it is critical for the triggering of GC formation and plays a modulatory role during the extension of the GC's lamellipodia. (C) 2002 Wiley Periodicals, Inc.