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Dev Cell. 2011 May 17;20(5):610-22. doi: 10.1016/j.devcel.2011.04.006.

Numb links extracellular cues to intracellular polarity machinery to promote chemotaxis.

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  • 1Department of Pediatric Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Abstract

Cell polarization is essential throughout development for proliferation, migration, and differentiation. However, it is not known how extracellular cues correctly orient cell polarity at distinct stages of development. Here, we show that the endocytic adaptor protein Numb, previously characterized for its role in cell proliferation, subsequently plays an important role in cell migration. In neural precursors stimulated with the chemotactic factor BDNF, Numb binds to activated TrkB, the BDNF receptor, and functions both as an endocytic regulator for TrkB and as a scaffold for aPKC (aPKC). Thus, Numb promotes BDNF-dependent aPKC activation. Interestingly, Numb is also a substrate of aPKC. When phosphorylated, Numb exhibits increased efficacy in binding TrkB and in promoting a chemotactic response to BDNF. Therefore, Numb functions in a feed-forward loop to promote chemotaxis of neural precursors, linking BDNF, an extracellular cue, to aPKC, a critical component of the intrinsic polarity machinery.

Copyright © 2011 Elsevier Inc. All rights reserved.

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PMID:
21571219
[PubMed - indexed for MEDLINE]
PMCID:
PMC3103748
Free PMC Article

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