A distal axonal cytoskeleton forms an intra-axonal boundary that controls axon initial segment assembly

Mauricio R. Galiano, Smita Jha, Tammy Szu Yu Ho, Chuansheng Zhang, Yasuhiro Ogawa, Kae Jiun Chang, Michael C. Stankewich, Peter J. Mohler, Matthew N. Rasband

Research output: Contribution to journalArticlepeer-review

189 Scopus citations

Abstract

AnkyrinG (ankG) is highly enriched in neurons at axon initial segments (AISs) where it clusters Na+ and K+ channels and maintains neuronal polarity. How ankG becomes concentrated at the AIS is unknown. Here, we show that as neurons break symmetry, they assemble a distal axonal submembranous cytoskeleton, comprised of ankyrinB (ankB), αII-spectrin, and βII-spectrin, that defines a boundary limiting ankG to the proximal axon. Experimentally moving this boundary altered the length of ankG staining in the proximal axon, whereas disruption of the boundary through silencing of ankB, αII-spectrin, or βII-spectrin expression blocked AIS assembly and permitted ankG to redistribute throughout the distal axon. In support of an essential role for the distal cytoskeleton in ankG clustering, we also found that αII and βII-spectrin-deficient mice had disrupted AIS. Thus, the distal axonal cytoskeleton functions as an intra-axonal boundary restricting ankG to the AIS.

Original languageEnglish (US)
Pages (from-to)1125-1139
Number of pages15
JournalCell
Volume149
Issue number5
DOIs
StatePublished - May 25 2012
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'A distal axonal cytoskeleton forms an intra-axonal boundary that controls axon initial segment assembly'. Together they form a unique fingerprint.

Cite this