Numb Cells Keep Moving

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Science  20 Jul 2007:
Vol. 317, Issue 5836, pp. 297
DOI: 10.1126/science.317.5836.297c

Integrins are heterodimeric transmembrane receptors that bind to components of the extracellular matrix and are important for both cellular adhesion and migration. The clustering of activated integrins on the substrate-facing surface of the leading edge of a cell results in the recruitment of various proteins, including actin stress fibers, to form a focal adhesion complex (FAC). Cells move, in part, through the coordinated assembly and disassembly of focal adhesions at the leading edge of the cell. Numb is a cargo-specific adaptor protein that binds to several endocytic proteins, and Nishimura et al. examined the role of Numb in endothelial and epithelial cell cultures. In a wound-healing assay, Numb polarized toward the leading edge of migrating cells (just behind the lamellipodium), and immunostaining demonstrated that Numb and β-integrin colocalized at focal adhesions. Coimmunoprecipitation experiments revealed that Numb bound to the PAR (for partitioning defective) polarization complex PAR-3. This complex also localizes to the leading edge of polarized migrating cells. One component of this complex, atypical protein kinase C (aPKC) phosphorylated Numb in HeLa cells and, as a consequence, Numb no longer bound to integrins. The authors propose that Numb binds to free integrin molecules (rather than disrupting FACs) and recruits them to clathrin-coated structures to initiate integrin recycling, and that the localization and function of Numb are negatively regulated by aPKC. — JFF

Dev. Cell 13, 15 (2007).

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