L1 Endocytosis

Science's STKE  02 Jul 2002:
Vol. 2002, Issue 139, pp. tw232-TW232
DOI: 10.1126/stke.2002.139.tw232

The neuronal cell adhesion molecule L1 regulates growth cone dynamics through extracellular interaction with other L1 molecules. Its cytoplasmic domain harbors a tyrosine-based sorting motif that interacts with the cell's clathrin machinery to facilitate its internalization. Schaefer et al. show that a single tyrosine residue within this motif is phosphorylated in vivo by the cytoplasmic tyrosine kinase Src. Phosphorylation prevented L1 binding to the adaptor protein AP-2 of the endocytosis machinery. L1-L1 interaction increased its dephosphorylation and increased its internalization into intracellular vesicles. The biochemical analysis suggests that cycles of phosphorylation and dephosphorylation regulate L1 availability in neurons.

A.W. Schaefer, Y. Kamei, H. Kamiguchi, E.V. Wong, I. Rapoport, T. Kirchhausen, C.M. Beach, G. Landreth, S.K. Lemmon, V. Lemmon, L1 endocytosis is controlled by a phosphorylation-dephosphorylation cycle stimulated by outside-in signaling by L1. J. Cell Biol. 157, 1223-1232 (2002). [Abstract] [Full Text]