The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins
Open accessAbstract
The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to αvβ5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by αvβ5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via αvβ5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions.
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Cited by
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Metadata
- Authors
- Mechtersheimer, S., Gutwein, P., Agmon-Levin, N., Stoeck, A., Oleszewski, M., Riedle, S., Postina, R., Fahrenholz, F., Fogel, M., Lemmon, V., & Altevogt, P.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2001-11-12
- Volume
- 155
- Issue
- 4
- Pages
- 661-674
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2137592112
- Cited by
- 391
- References
- 62
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- green
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- Mechtersheimer, S., Gutwein, P., Agmon-Levin, N., Stoeck, A., Oleszewski, M., Riedle, S., Postina, R., Fahrenholz, F., Fogel, M., Lemmon, V., & Altevogt, P. (2001). Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200101099
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