ABSENCE OF PERSISTENT SPREADING, BRANCHING, AND ADHESION IN GAP-43-DEPLETED GROWTH CONES

被引:167
作者
AIGNER, L [1 ]
CARONI, P [1 ]
机构
[1] FRIEDRICH MIESCHER INST,CH-4002 BASEL,SWITZERLAND
关键词
D O I
10.1083/jcb.128.4.647
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The growth-associated protein GAP-43 is a major protein kinase C substrate of growth cones and developing nerve terminals. In the: growth cone, it accumulates near the plasma membrane, where it associates with the cortical cytoskeleton and membranes. The role of GAP-43 in neurite outgrowth is not yet clear, but recent findings suggest that it may be a crucial competence factor in this process. To define the role of GAP-43 in growth cone activity, we have analyzed neurite outgrowth and growth cone activity in primary sensory neurons depleted of GAP-43 by a specific antisense oligonucleotide procedure. Under optimal culture conditions, but in the absence of GAP-43, growth cones adhered poorly, displayed highly dynamic but unstable lamellar extensions, and were strikingly devoid of local f-actin concentrations. Upon stimulation, they failed to produce NGF-induced spreading or insulin-like growth factor-1-induced branching, whereas growth factor-induced phosphotyrosine immunoreactivity and acceleration of neurite elongation were not impaired. Unlike their GAP-43-expressing counterparts, they readily retracted when exposed to inhibitory central nervous system myelin-derived liposomes. Frequency and extent of induced retraction were attenuated by NGF. Our results indicate that GAP-43 can promote f-actin accumulation, evoked morphogenic activity, and resistance to retraction of the growth cone, suggesting that it may promote regulated neurite outgrowth during development and regeneration.
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页码:647 / 660
页数:14
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