Flotillin-mediated endocytic events dictate cell type-specific responses to semaphorin 3A.
Flotillin-mediated endocytic events dictate cell type-specific responses to semaphorin 3A.
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DOI：
10.1523/jneurosci.1821-10.2010
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发表时间：
2010-11-10
期刊：
影响因子：
--
通讯作者：
Benson DL
中科院分区：
文献类型：
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作者：
Carcea I;Ma'ayan A;Mesias R;Sepulveda B;Salton SR;Benson DL
Cortical efferents growing in the same environment diverge early in development. The expression of particular transcription factors dictates the trajectories taken presumably by regulating responsiveness to guidance cues via cellular mechanisms that are not yet known. Here we show that cortical neurons that are dissociated and grown in culture maintain their cell-type specific identities defined by the expression of transcription factors. Using this model system we sought to identify and characterize mechanisms that are recruited to produce cell-type specific responses to Semaphorin 3A (Sema3A), a guidance cue that would be presented similarly to cortical axons in vivo. Axons from presumptive corticofugal neurons lacking the transcription factor Satb2 and expressing Ctip2 or Tbr1 respond far more robustly to Sema3A than those from presumptive callosal neurons expressing Satb2. Both populations of axons express similar levels of Sema3A receptors (Neuropilin-1, L1CAM and PlexinA4), but significantly, axons from neurons lacking Satb2 internalize more Sema3A and they do so via a raft-mediated endocytic pathway. We used an in silico approach to identify the endocytosis effector Flotillin-1 as a Sema3A signaling candidate. We tested the contributions of Flotillin-1 to Sema3A endocytosis and signaling, and show that raft-mediated Sema3A endocytosis is defined by and depends on the recruitment of Flotillin-1, which mediates LIMK activation, and regulates axon responsiveness to Sema3A in presumptive corticofugal axons.
