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© The Rockefeller University Press, 0021-9525/1999/9/1173/ $5.00
The Journal of Cell Biology, Volume 146, Number 5, September 6, 1999 1173-1184

Heterophilic Binding of L1 on Unmyelinated Sensory Axons Mediates Schwann Cell Adhesion and Is Required for Axonal Survival

C.A. Haneya,b, Z. Sahenkc, C. Lid, V.P. Lemmona, J. Roderd, and B.D. Trappa,b
a Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106
b Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195
c Department of Neurology, Neuromuscular Disease Center, College of Medicine, Ohio State University, Columbus, Ohio 43210
d Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Department of Molecular and Medical Genetics, University of Toronto, Toronto, Canada

Correspondence to: B.D. Trapp, Department of Neurosciences, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. Tel:(216) 444-7177 Fax:(216) 444-7927 E-mail:trappb{at}ccf.org.

This study investigated the function of the adhesion molecule L1 in unmyelinated fibers of the peripheral nervous system (PNS) by analysis of L1- deficient mice. We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmyelinated fibers. In L1-deficient sensory nerves, Schwann cells formed but failed to retain normal axonal ensheathment. L1-deficient mice had reduced sensory function and loss of unmyelinated axons, while sympathetic unmyelinated axons appeared normal. In nerve transplant studies, loss of axonal-L1, but not Schwann cell-L1, reproduced the L1-deficient phenotype. These data establish that heterophilic axonal-L1 interactions mediate adhesion between unmyelinated sensory axons and Schwann cells, stabilize the polarization of Schwann cell surface membranes, and mediate a trophic effect that assures axonal survival.

Key Words: cell adhesion, cell polarity, axonal degeneration, L1, myelin-associated glycoprotein


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