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Scaffolds from blood to brain

The thick scaffold beneath the NR membrane (arrow, top) is missing in neurons lacking ßIV1 spectrin (bottom).

Scaffolds that hold up membrane proteins in red blood cells also support the channels needed for neuronal signaling, as shown by Lacas-Gervais et al. on page 983.

Neurons fire when sodium channels clustered at the axonal initial segment (AIS) open. This depolarization is propagated by more channels clustered along axons in the Nodes of Ranvier (NR). The structure of these compartments is now shown to rely on a spectrin, relatives of which are needed for the characteristic concave shape of the red blood cell plasma membrane.

The AIS and NR are rich in two spectrins: ßIV1 and ßIV6. But loss of the ßIV1 isoform was sufficient to disrupt AIS and NR physiology. NRs in the mutants were longer and fatter and lacked the protein-dense region beneath the NR membrane, which probably corresponds to the ßIV1 scaffold. These changes interfered with membrane potential generation and propagation, thus causing deafness.

Recent results showed that sodium channels are concentrated in the AIS because of both anchoring to the AIS cytoskeleton and endocytosis elsewhere. The specialized AIS cytoskeleton may prevent endocytosis at this site. In the ßIV1 mutants, the NR contained membrane protrusions that were filled with vesicular organelles. If spectrins are involved in membrane trafficking, as has been proposed, the vesicles may be a result of increased endocytosis in the mutant NR.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Related Article

ßIV1 spectrin stabilizes the nodes of Ranvier and axon initial segments

Sandra Lacas-Gervais, Jun Guo, Nicola Strenzke, Eric Scarfone, Melanie Kolpe, Monika Jahkel, Pietro De Camilli, Tobias Moser, Matthew N. Rasband, and Michele Solimena
J. Cell Biol. 2004 166: 983-990. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 874K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?