title: Numb links extracellular cues to intracellular polarity machinery to promote chemotaxis.
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.
authors.affiliation: Department of Pediatric Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhou
authors.forename: Jose
authors.initials: J
authors.lastname: Alfaro
authors.forename: Eun Hyuk
authors.initials: EH
authors.lastname: Chang
authors.forename: Xuesong
authors.initials: X
authors.lastname: Zhao
authors.forename: Marimelia
authors.initials: M
authors.lastname: Porcionatto
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Segal
mesh_terms: D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism
chemical_list: D002630:Chemotactic Factors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; D020813:Receptor, trkB; C115015:PKC-3 protein; D011493:Protein Kinase C