Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins

Sabine Mechtersheimer, Paul Gutwein, Nancy Agmon-Levin, Alexander Stoeck, Matthias Oleszewski, Svenja Riedle, Rolf Postina, Falk Fahrenholz, Mina Fogel, Vance Lemmon, Peter Altevogt

Research output: Contribution to journalArticle

288 Citations (Scopus)

Abstract

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 alpha v beta 5 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 alpha v beta 5-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 alpha v beta 5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions.

Original languageEnglish
Pages (from-to)661-673
Number of pages13
JournalThe Journal of cell biology
Volume155
Issue number4
StatePublished - Nov 12 2001
Externally publishedYes

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CHO Cells
Integrins
Cell Movement
Metalloproteases
Physiological Phenomena
Disintegrins
Biological Phenomena
Antibodies
Fibrinolysin
Laminin
Fibronectins
Nervous System
Transfection
Carcinoma
Membranes
Brain
Neoplasms
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mechtersheimer, S., Gutwein, P., Agmon-Levin, N., Stoeck, A., Oleszewski, M., Riedle, S., ... Altevogt, P. (2001). Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. The Journal of cell biology, 155(4), 661-673.

Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. / Mechtersheimer, Sabine; Gutwein, Paul; Agmon-Levin, Nancy; Stoeck, Alexander; Oleszewski, Matthias; Riedle, Svenja; Postina, Rolf; Fahrenholz, Falk; Fogel, Mina; Lemmon, Vance; Altevogt, Peter.

In: The Journal of cell biology, Vol. 155, No. 4, 12.11.2001, p. 661-673.

Research output: Contribution to journalArticle

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, vol. 155, no. 4, pp. 661-673.
Mechtersheimer S, Gutwein P, Agmon-Levin N, Stoeck A, Oleszewski M, Riedle S et al. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. The Journal of cell biology. 2001 Nov 12;155(4):661-673.
Mechtersheimer, Sabine ; Gutwein, Paul ; Agmon-Levin, Nancy ; Stoeck, Alexander ; Oleszewski, Matthias ; Riedle, Svenja ; Postina, Rolf ; Fahrenholz, Falk ; Fogel, Mina ; Lemmon, Vance ; Altevogt, Peter. / Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. In: The Journal of cell biology. 2001 ; Vol. 155, No. 4. pp. 661-673.
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