TY - JOUR T1 - L1 Enhances Autocrine-Dependent Migration JF - Science's STKE JO - Sci. STKE SP - tw428 LP - tw428 DO - 10.1126/stke.2001.109.tw428 VL - 2001 IS - 109 A2 - , Y1 - 2001/11/20 UR - http://stke.sciencemag.org/content/2001/109/tw428.abstract N2 - The L1 adhesion molecule enhances the migration of neural and immune cells. L1 can be proteolytically cleaved by metalloproteinases, but the importance of this has been unclear. Now, Mechtersheimer et al. have found that proteolytic cleavage of the ectodomain of L1 promotes cell migration. Chinese hamster ovary (CHO) cells expressing L1 (L1-CHO) exhibited enhanced migration compared with that of untransfected CHO cells; however, enhanced migration was decreased to basal levels by treating the cells with metalloproteinase inhibitors, suggesting that proteolytic cleavage of L1 promoted cell migration. The enhanced migration of L1-CHO cells was also decreased when cells were treated with antibodies to the integrin αvβ5; however, untransfected CHO cells treated with αvβ5-specific antibodies did not exhibit decreased normal migration, suggesting that LI and αvβ5 might be in the same signaling pathway that leads to enhanced cell migration. Additionally, untransfected CHO cells incubated in conditioned medium derived from L1-CHO, but not CHO, cell culture showed enhanced migration; the enhancement depended on the presence of the conserved integrin-binding motif arginine-glycine-aspartate in L1, indicating that soluble L1 may increase cell migration through interactions with αvβ5. Overexpression of a dominant-negative form of the metalloproteinase ADAM10 reduced the extracellular proteolysis of L1 in L1-CHO cells. Thus, L1 appears to promote enhanced migration through an autocrine process that involves the binding of the soluble cleaved L1 ectodomain to specific integrins on the cell surface. S. Mechtersheimer, P. Gutwein, N. Agmon-Levin, A. Stoeck, M. Oleszewski, S. Riedle, M. Fogel, V. Lemmon, P. Altevogt, Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. J. Cell Biol. 155, 661-674 (2001). [Abstract] [Full Text] ER -