ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and in released membrane vesicles

SPECIFIC AIMSL1, an important molecule for cell migration of neural and tumor cells, is released by membrane-proximal cleavage and soluble L1 promotes cell migration. Since previous studies have implicated a role of ADAM10 in L1 release, we examined the localization of L1 and ADAM10 and the mode of cleavage.PRINCIPAL FINDINGS1. ADAM10 mediates cleavage of the L1 ectodomainWe reinvestigated the cleavage of L1 in HEK293 cells, which do not express L1 but are positive for ADAM10. Expression of human L1 in these cells allowed detection of soluble L1–200 in the medium. Overexpression of ADAM10 in combination with L1 enhanced the release of soluble L1. In contrast, HEK293 cells cotransfected with L1 and dominant-negative ADAM10 showed a reduction of L1 shedding as detected by a decrease in soluble L1–200 and L1–32, which represents the membrane retained cleavage fragment.2. Subcellular localization of L1 and ADAM10We studied in more detail the localization of L1 and ADAM10 using an antibody to the extracellular...