Endocytosis of beta1 integrins is an early event in migration promoted by the cell adhesion molecule L1.

@article{citeulike:2193998, abstract = {Directional cell motility is a complex process requiring orchestration of signals from diverse cell adhesion receptors for proper organization of neuronal groups in the brain. The L1 cell adhesion molecule potentiates integrin-dependent migration of neuronal cells and stimulates integrin endocytosis but its mechanism of action is unclear. The hypothesis was investigated that L1 stimulates cell motility by modulating surface levels of integrins through intracellular trafficking using a model cell system. Antibody-induced clustering of L1, which mimics ligand binding, induced formation of cell surface complexes of L1 and beta1 integrins in L1-expressing HEK293 cells. L1 formed cell surface complexes with integrin beta1 and alpha3 subunits but not with integrin alpha1. Following cell surface clustering, beta1 integrins and L1 became rapidly internalized into Rab5+ early endosomes. Internalization of L1 and beta1 integrins was prevented by treatment with monodansyl cadaverine (MDC), an inhibitor of clathrin-dependent endocytosis, and by deletion of the AP2/clathrin binding motif (RSLE) from the L1 cytoplasmic domain. MDC treatment coordinately inhibited L1-potentiated haptotactic migration of HEK293 cells to fibronectin in Transwell assays. These results suggested that downregulation of adhesive complexes of L1 and beta1 integrin at the plasma membrane by clathrin-mediated endocytosis is a potential mechanism for enhancing cell motility.}, address = {Department of Biochemistry and Biophysics, 505 Mary Ellen Jones Bldg, CB\#7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260, USA.}, author = {Panicker, A. K. and Buhusi, M. and Erickson, A. and Maness, P. F. }, citeulike-article-id = {2193998}, doi = {10.1016/j.yexcr.2005.10.031}, issn = {0014-4827}, journal = {Exp Cell Res}, keywords = {adhesion, ankyrin, axon\_guidance, l1, transgenic}, month = {February}, number = {3}, pages = {299--307}, posted-at = {2008-01-04 09:47:40}, priority = {0}, title = {Endocytosis of beta1 integrins is an early event in migration promoted by the cell adhesion molecule L1.}, url = {http://dx.doi.org/10.1016/j.yexcr.2005.10.031}, volume = {312}, year = {2006} }

TY - JOUR ID - citeulike:2193998 L3 - citeulike-article-id:2193998 TI - Endocytosis of beta1 integrins is an early event in migration promoted by the cell adhesion molecule L1. JF - Exp Cell Res VL - 312 IS - 3 SP - 299 EP - 307 AD - Department of Biochemistry and Biophysics, 505 Mary Ellen Jones Bldg, CB#7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260, USA. SN - 0014-4827 N2 - Directional cell motility is a complex process requiring orchestration of signals from diverse cell adhesion receptors for proper organization of neuronal groups in the brain. The L1 cell adhesion molecule potentiates integrin-dependent migration of neuronal cells and stimulates integrin endocytosis but its mechanism of action is unclear. The hypothesis was investigated that L1 stimulates cell motility by modulating surface levels of integrins through intracellular trafficking using a model cell system. Antibody-induced clustering of L1, which mimics ligand binding, induced formation of cell surface complexes of L1 and beta1 integrins in L1-expressing HEK293 cells. L1 formed cell surface complexes with integrin beta1 and alpha3 subunits but not with integrin alpha1. Following cell surface clustering, beta1 integrins and L1 became rapidly internalized into Rab5+ early endosomes. Internalization of L1 and beta1 integrins was prevented by treatment with monodansyl cadaverine (MDC), an inhibitor of clathrin-dependent endocytosis, and by deletion of the AP2/clathrin binding motif (RSLE) from the L1 cytoplasmic domain. MDC treatment coordinately inhibited L1-potentiated haptotactic migration of HEK293 cells to fibronectin in Transwell assays. These results suggested that downregulation of adhesive complexes of L1 and beta1 integrin at the plasma membrane by clathrin-mediated endocytosis is a potential mechanism for enhancing cell motility. KW - adhesion KW - ankyrin KW - axon_guidance KW - l1 KW - transgenic AU - Panicker, AK AU - Buhusi, M AU - Erickson, A AU - Maness, PF PY - 2006/02/01/ UR - http://dx.doi.org/10.1016/j.yexcr.2005.10.031 ER -