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Proc Natl Acad Sci U S A. 2018 Mar 13;115(11):2764-2769. doi: 10.1073/pnas.1711667115. Epub 2018 Feb 26.

Grip and slip of L1-CAM on adhesive substrates direct growth cone haptotaxis.

Author information

1
Laboratory of Systems Neurobiology and Medicine, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma 630-0192, Japan.
2
Laboratory of Structural Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma 630-0192, Japan.
3
Division of Regenerative Medicine, Institute for Clinical Research, Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Osaka 540-0006, Japan.
4
Department of Applied Chemistry, Graduate School of Engineering, University of Tokyo, Tokyo 113-8656, Japan.
5
Laboratory of Systems Neurobiology and Medicine, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma 630-0192, Japan; ninagaki@bs.naist.jp.

Abstract

Chemical cues presented on the adhesive substrate direct cell migration, a process termed haptotaxis. To migrate, cells must generate traction forces upon the substrate. However, how cells probe substrate-bound cues and generate directional forces for migration remains unclear. Here, we show that the cell adhesion molecule (CAM) L1-CAM is involved in laminin-induced haptotaxis of axonal growth cones. L1-CAM underwent grip and slip on the substrate. The ratio of the grip state was higher on laminin than on the control substrate polylysine; this was accompanied by an increase in the traction force upon laminin. Our data suggest that the directional force for laminin-induced growth cone haptotaxis is generated by the grip and slip of L1-CAM on the substrates, which occur asymmetrically under the growth cone. This mechanism is distinct from the conventional cell signaling models for directional cell migration. We further show that this mechanism is disrupted in a human patient with L1-CAM syndrome, suffering corpus callosum agenesis and corticospinal tract hypoplasia.

KEYWORDS:

axon guidance; cell adhesion; cell migration; clutch; shootin1

PMID:
29483251
PMCID:
PMC5856512
DOI:
10.1073/pnas.1711667115
[Indexed for MEDLINE]
Free PMC Article

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