LKB1/STRAD promotes axon initiation during neuronal polarization

被引：285

作者：

Shelly, Maya ^{[1
]}

Cancedda, Laura ^{[1
]}

Heilshorn, Sarah ^{[1
]}

Sumbre, German ^{[1
]}

Poo, Mu-ming ^{[1
]}

机构：

[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Div Neurobiol, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA

来源：

CELL | 2007年 / 129卷 / 03期

关键词：

D O I：

10.1016/j.cell.2007.04.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Axon/dendrite differentiation is a critical step in neuronal development. In cultured hippocampal neurons, the accumulation of LKB1 and STRAD, two interacting proteins critical for establishing epithelial polarity, in an undifferentiated neurite correlates with its subsequent axon differentiation. Downregulation of either LKB1 or STRAD by siRNAs prevented axon differentiation, and overexpression of these proteins led to multiple axon formation. Furthermore, interaction of STRAD with LKB1 promoted LKB1 phosphorylation at a PKA site S431 and elevated the LKB1 level, and overexpressing LKB1 with a serine-to-alanine mutation at S431 (LKB1 S431 A) prevented axon differentiation. In developing cortical neurons in vivo, downregulation of LKB1 or overexpression of LKB1 S431 A also abolished axon formation. Finally, local exposure of the undifferentiated neurite to brain-derived neurotrophic factor or dibutyryl-cAMP promoted axon differentiation in a manner that depended on PKA-depenclent LKB1 phosphorylation. Thus local LKB1/STRAD accumulation and PKA-dependent LKB1 phosphorylation represents an early signal for axon initiation.

引用

页码：565 / 577

页数：13

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