Transmembrane agrin regulates filopodia in rat hippocampal neurons in culture

被引:42
作者
McCroskery, Seumas [1 ]
Chaudhry, Amal [1 ]
Lin, Lin [1 ]
Daniels, Mathew P. [1 ]
机构
[1] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1016/j.mcn.2006.06.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Filopodia mediate axon guidance, neurite branching and synapse formation, but the membrane molecules that regulate neuronal filopodia in response to extracellular cues are largely unknown. The transmembrane isoform of the proteoglycan agrin, expressed predominantly in the CNS, may regulate neurite outgrowth, synapse formation and excitatory signaling. Here we demonstrate that agrin positively regulates neuronal filopodia. Over-expression of TM-agrin caused the formation of excess filopodia on neurites of hippocampal neurons cultured 1-6 days. Conversely, suppression of agrin expression by siRNA reduced the number of filopodia. Time lapse analysis indicated that endogenous TM-agrin regulates filopodia by increasing their stability and initiation. The N-terminal half of agrin was necessary for induction of filopodia, and over-expression of TM-agrin in a neuronal cell line increased Cdc42 activation, suggesting a role for Cdc42 downstream of agrin. By positively regulating filopodia in developing neurons, TM-agrin may influence the pattern of neurite outgrowth and synapse formation. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:15 / 28
页数:14
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