title: betaIV-spectrin forms a diffusion barrier against L1CAM at the axon initial segment.
abstract: Axonal and somatodendritic plasma membranes of polarized neurons express distinct sets of functional molecules. It is known that the neuronal polarity can be maintained by a barrier that impedes diffusional mixing of membrane components between the two domains. Using betaIV-spectrin knockout mice, we demonstrate the involvement of this cytoskeletal protein in the formation of a barrier that selectively blocks lateral mobility of L1 cell adhesion molecule (L1CAM) at the axon initial segment of hippocampal neurons. We also show that the betaIV-spectrin-based barrier is required for the axon-specific distribution of L1CAM both in vitro and in vivo. The barrier activity against L1CAM may depend on direct interactions of L1CAM with ankyrinG, a protein binding to betaIV-spectrin, rather than on steric hindrance by other transmembrane proteins clustered at the axon initial segment. Our results highlight the role of betaIV-spectrin and ankyrinG as critical components of a selective barrier against L1CAM.
authors.affiliation: Laboratory for Neuronal Growth Mechanisms, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Nishimura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Akiyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Komada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiguchi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D013049:Spectrin / Q000172:deficiency / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; C417303:betaIV spectrin; D013049:Spectrin