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XB-ART-36104
J Cell Biol July 2, 2007; 178 (1): 107-19.

BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin.

Wen Z , Han L , Bamburg JR , Shim S , Ming GL , Zheng JQ .


Abstract
Bone morphogenic proteins (BMPs) are involved in axon pathfinding, but how they guide growth cones remains elusive. In this study, we report that a BMP7 gradient elicits bidirectional turning responses from nerve growth cones by acting through LIM kinase (LIMK) and Slingshot (SSH) phosphatase to regulate actin-depolymerizing factor (ADF)/cofilin-mediated actin dynamics. Xenopus laevis growth cones from 4-8-h cultured neurons are attracted to BMP7 gradients but become repelled by BMP7 after overnight culture. The attraction and repulsion are mediated by LIMK and SSH, respectively, which oppositely regulate the phosphorylation-dependent asymmetric activity of ADF/cofilin to control the actin dynamics and growth cone steering. The attraction to repulsion switching requires the expression of a transient receptor potential (TRP) channel TRPC1 and involves Ca2+ signaling through calcineurin phosphatase for SSH activation and growth cone repulsion. Together, we show that spatial regulation of ADF/cofilin activity controls the directional responses of the growth cone to BMP7, and Ca2+ influx through TRPC tilts the LIMK-SSH balance toward SSH-mediated repulsion.

PubMed ID: 17606869
PMC ID: PMC2064427
Article link: J Cell Biol
Grant support: [+]
Genes referenced: actl6a bmp7.1 bmp7.2 bmpr2 ctrl dstn fst grap2 hspa9 inhbc.1 limk1 nog ppp3ca trpc1


Article Images: [+] show captions
References [+] :
Aizawa, Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse. 2001, Pubmed


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