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Mol Cell Neurosci. 2007 Mar;34(3):422-30. Epub 2007 Jan 16.

betaIV-spectrin forms a diffusion barrier against L1CAM at the axon initial segment.

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Laboratory for Neuronal Growth Mechanisms, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.


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.

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