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BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin.
- Source :
-
The Journal of cell biology [J Cell Biol] 2007 Jul 02; Vol. 178 (1), pp. 107-19. - Publication Year :
- 2007
-
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.
- Subjects :
- Animals
Blastomeres metabolism
Bone Morphogenetic Protein 7
Calcium metabolism
Calcium Signaling
Destrin genetics
Embryo, Nonmammalian
Ganglia, Spinal cytology
Lim Kinases
Microinjections
Models, Biological
Neurons cytology
Neurons metabolism
RNA, Messenger administration & dosage
TRPC Cation Channels metabolism
Xenopus embryology
Xenopus Proteins metabolism
Bone Morphogenetic Proteins metabolism
Cofilin 1 metabolism
Destrin metabolism
Growth Cones physiology
Phosphoric Monoester Hydrolases metabolism
Protein Kinases metabolism
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9525
- Volume :
- 178
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 17606869
- Full Text :
- https://doi.org/10.1083/jcb.200703055