Myelin basic protein cleaves cell adhesion molecule L1 and promotes neuritogenesis and cell survival [Cell Biology]

March 26th, 2014 by Lutz, D., Loers, G., Kleene, R., Oezen, I., Kataria, H., Katagihallimath, N., Braren, I., Harauz, G., Schachner, M.

ABSTRACT The cell adhesion molecule L1 is a Lewisx- carrying glycoprotein which plays important roles in the developing and adult nervous system.Here, we show that myelin basic protein (MBP)binds to L1 in a Lewisx-dependent manner. Furthermore,we demonstrate that MBP is released by murinecerebellar neurons as a sumoylated dynamin - containing protein upon L1 stimulation and that this MBP cleaves L1 as a serine protease in the L1 extracellular domain at Arg687 yielding a transmembrane fragment which promotes neurite outgrowth and neuronal survival in cell culture. L1-induced neurite outgrowth and neuronalsurvival are reduced in MBP-deficient cerebellar neurons,and in wild -type cerebellar neurons in the presence of an MBP antibody or L1 peptide containing the MBP cleavage site. Genetic ablation of MBP in shiverer mice, mutagenesis of the proteolytically active site in MBP or of the MBP cleavage site within L1, as well as serine protease inhibitors and an L1 peptide containing the MBP cleavage site abolish generation of the L1 fragment. Our findings provide evidence for novel functions of MBP in the nervous system