beta IV-spectrin forms a diffusion barrier against L1CAM at the axon initial segment

摘要

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 PIV-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 (LICAM) at the axon initial segment of hippocampal neurons. We also show that the beta IV-spectrin-based barrier is required for the axon-specific distribution of L1ACAM both in vitro and in vivo. The barrier activity against L1ACAM may depend on direct interactions of L1CAM with ankyrin(G), a protein binding to PIV-spectrin, rather than on steric hindrance by other transmembrane proteins clustered at the axon initial segment. Our results highlight the role of PIV-spectrin and ankyrin(G) as critical components of a selective barrier against L1CAM. (c) 2006 Elsevier Inc. All rights reserved.