期刊
CELL
卷 129, 期 3, 页码 579-591出版社
CELL PRESS
DOI: 10.1016/j.cell.2007.03.023
关键词
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资金
- NCRR NIH HHS [P41 RR04050, P41 RR004050] Funding Source: Medline
- NINDS NIH HHS [R01 NS014718, P30 NS047101-03S1, K02 NS042749-05, R01 NS041537-05, R01 NS041537, R01 NS14718, K02 NS042749, P30 NS047101-04, P30 NS047101] Funding Source: Medline
The axonal shafts of neurons contain bundled microtubules, whereas extending growth cones contain unbundled microtubule filaments, suggesting that localized activation of microtubule-associated proteins (MAP) at the transition zone may bundle these filaments during axonal growth. Dephosphorylation is thought to lead to MAP activation, but specific molecular pathways have remained elusive. We find that Spinophilin, a Protein-phosphatase 1 (PP1) targeting protein, is responsible for the dephosphorylation of the MAP Doublecortin (Dcx) Ser 297 selectively at the wrist of growing axons, leading to activation. Loss of activity at the wrist is evident as an impaired microtubule cytoskeleton along the shaft. These findings suggest that spatially restricted adaptor-specific MAP reactivation through dephosphorylation is important in organization of the neuronal cytoskeleton.
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