The first two authors contributed equally to this work.
Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain development
Article first published online: 20 NOV 2009
Copyright © 2009 Wiley-Liss, Inc.
Journal of Comparative Neurology
Volume 518, Issue 7, pages 1113–1132, 1 April 2010
How to Cite
Nakamura, Y., Lee, S., Haddox, C. L., Weaver, E. J. and Lemmon, V. P. (2010), Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain development. J. Comp. Neurol., 518: 1113–1132. doi: 10.1002/cne.22267
- Issue published online: 1 FEB 2010
- Article first published online: 20 NOV 2009
- Accepted manuscript online: 20 NOV 2009 12:00AM EST
- Manuscript Accepted: 29 OCT 2009
- Manuscript Revised: 18 SEP 2009
- Manuscript Received: 31 JUL 2009
- National Institutes of Health. Grant Number: HD39884
- Miami Project to Cure Paralysis
- RIKEN Brain Science Institute
- axon guidance;
Mutations in the human L1CAM gene cause X-linked hydrocephalus and MASA (Mental retardation, Aphasia, Shuffling gait, Adducted thumbs) syndrome. In vitro studies have shown that the L1 cytoplasmic domain (L1CD) is involved in L1 trafficking, neurite branching, signaling, and interactions with the cytoskeleton. L1cam knockout (L1KO) mice have hydrocephalus, a small cerebellum, hyperfasciculation of corticothalamic tracts, and abnormal peripheral nerves. To explore the function of the L1CD, we made three new mice lines in which different parts of the L1CD have been altered. In all mutant lines L1 protein is expressed and transported into the axon. Interestingly, these new L1CD mutant lines display normal brain morphology. However, the expression of L1 protein in the adult is dramatically reduced in the two L1CD mutant lines that lack the ankyrin-binding region and they show defects in motor function. Therefore, the L1CD is not responsible for the major defects observed in L1KO mice, yet it is required for continued L1 protein expression and motor function in the adult. J. Comp. Neurol. 518:1113–1132, 2010. © 2009 Wiley-Liss, Inc.