TY - JOUR
T1 - A distal axonal cytoskeleton forms an intra-axonal boundary that controls axon initial segment assembly
AU - Galiano, Mauricio R.
AU - Jha, Smita
AU - Ho, Tammy Szu Yu
AU - Zhang, Chuansheng
AU - Ogawa, Yasuhiro
AU - Chang, Kae Jiun
AU - Stankewich, Michael C.
AU - Mohler, Peter J.
AU - Rasband, Matthew N.
N1 - Funding Information:
We thank Dr. Ed Cooper and the Rasband lab for discussions and critical reading of the manuscript. This research was supported by NIH grants NS044916 (M.N.R.), NS069688 (M.N.R.), HL083422 (P.J.M.), and HL084583 (P.J.M.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and Mission Connect. The generation of the SPNB2 fl/fl mice was supported in part by Baylor College of Medicine IDDRC Grant Number 5P30HD024064-23 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health & Human Development or the National Institutes of Health.
PY - 2012/5/25
Y1 - 2012/5/25
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2012.03.039
DO - 10.1016/j.cell.2012.03.039
M3 - Article
C2 - 22632975
AN - SCOPUS:84861534003
SN - 0092-8674
VL - 149
SP - 1125
EP - 1139
JO - Cell
JF - Cell
IS - 5
ER -