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

Proceedings of the National Academy of Sciences of the United States of America
Kouki AbeNaoyuki Inagaki

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.

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Citations

Sep 15, 2020·Advanced Biosystems·Hiroshi SunamiYasuyuki Igarashi
May 28, 2019·The Journal of Cell Biology·Xiao-Feng ZhangPaul Forscher
Sep 29, 2020·Frontiers in Cell and Developmental Biology·Takunori Minegishi, Naoyuki Inagaki
Mar 14, 2021·Scientific Reports·Marie VersaevelSylvain Gabriele
Aug 14, 2021·Biophysical Journal·Kouki AbeNaoyuki Inagaki

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Methods Mentioned

BETA
Fluorescence

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