Shared and unique roles of CAP23 and GAP43 in actin regulation, neurite outgrowth, and anatomical plasticity.

Shared and unique roles of CAP23 and GAP43 in actin regulation, neurite outgrowth, and anatomical plasticity.
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DOI:
10.1083/jcb.149.7.1443
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发表时间:
2000-06-26
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Caroni P
Caroni P
中科院分区:
其他
文献类型:
--
作者:
Frey D;Laux T;Xu L;Schneider C;Caroni P

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CAP23是一种主要的皮质细胞因子相关和钙调蛋白结合蛋白,其在发育过程中广泛且大量表达,在成人的选定脑结构中维持,并在神经再生过程中重新诱导。CAP23在转基因小鼠的成年神经元中的过表达促进了神经出芽,但这种蛋白在过程生长中的作用尚不清楚。在这里,我们发现CAP23在功能上与GAP 43相关,并且在调节神经出芽和肌动蛋白细胞骨架中起着关键作用。缺乏CAP 23的敲除小鼠表现出明显而复杂的表型,包括在成年神经肌肉接头处产生刺激诱导的神经发芽的缺陷。这种发芽缺陷被拯救的转基因过表达的CAP 23或GAP 43在成年运动神经元。表达GAP 43而不是CAP 23的敲入小鼠基本上是正常的,这表明,尽管这些蛋白质不共享同源序列,但GAP 43可以在体内功能上替代CAP 23。培养的感觉神经元缺乏CAP 23表现出显着的神经突起生长的变化,这是由低剂量的细胞松弛素D表型模仿。对这种培养物的详细分析揭示了CAP 23和GAP 43对肌动蛋白细胞骨架和神经突生长的共同和独特功能。结果提供了令人信服的实验证据的概念,CAP 23和GAP 43是功能相关的内在决定因素的解剖可塑性,并建议这些蛋白质的功能,通过局部促进质膜下肌动蛋白细胞骨架积累。
CAP23 is a major cortical cytoskeleton–associated and calmodulin binding protein that is widely and abundantly expressed during development, maintained in selected brain structures in the adult, and reinduced during nerve regeneration. Overexpression of CAP23 in adult neurons of transgenic mice promotes nerve sprouting, but the role of this protein in process outgrowth was not clear. Here, we show that CAP23 is functionally related to GAP43, and plays a critical role to regulate nerve sprouting and the actin cytoskeleton. Knockout mice lacking CAP23 exhibited a pronounced and complex phenotype, including a defect to produce stimulus-induced nerve sprouting at the adult neuromuscular junction. This sprouting deficit was rescued by transgenic overexpression of either CAP23 or GAP43 in adult motoneurons. Knockin mice expressing GAP43 instead of CAP23 were essentially normal, indicating that, although these proteins do not share homologous sequences, GAP43 can functionally substitute for CAP23 in vivo. Cultured sensory neurons lacking CAP23 exhibited striking alterations in neurite outgrowth that were phenocopied by low doses of cytochalasin D. A detailed analysis of such cultures revealed common and unique functions of CAP23 and GAP43 on the actin cytoskeleton and neurite outgrowth. The results provide compelling experimental evidence for the notion that CAP23 and GAP43 are functionally related intrinsic determinants of anatomical plasticity, and suggest that these proteins function by locally promoting subplasmalemmal actin cytoskeleton accumulation.
CAP-23的鉴定,定位和主要结构,这是一种早期发育的粒子结合的胞质蛋白。
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作者:
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发表时间: 1995-02-10
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影响因子: 64.5
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发表时间: 1995-10-20
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影响因子: 64.5
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