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AnkyrinG is required for maintenance of the axon initial segment and neuronal polarity
Correspondence to Matthew N. Rasband: Rasband{at}bcm.edu
The axon initial segment (AIS) functions as both a physiological and physical bridge between somatodendritic and axonal domains. Given its unique molecular composition, location, and physiology, the AIS is thought to maintain neuronal polarity. To identify the molecular basis of this AIS property, we used adenovirus-mediated RNA interference to silence AIS protein expression in polarized neurons. Some AIS proteins are remarkably stable with half-lives of at least 2 wk. However, silencing the expression of the cytoskeletal scaffold ankyrinG (ankG) dismantles the AIS and causes axons to acquire the molecular characteristics of dendrites. Both cytoplasmic- and membrane-associated proteins, which are normally restricted to somatodendritic domains, redistribute into the former axon. Furthermore, spines and postsynaptic densities of excitatory synapses assemble on former axons. Our results demonstrate that the loss of ankG causes axons to acquire the molecular characteristics of dendrites; thus, ankG is required for the maintenance of neuronal polarity and molecular organization of the AIS.
Y. Ogawa's present address is Dept. of Pharmacology, Meiji Pharmaceutical University, Tokyo 204-8588, Japan.
Abbreviations used in this paper: AIS, axon initial segment; ankG, ankyrinG; CAM, cell adhesion molecule; DIV, day in vitro; DPI, day post infection; DPT, day post treatment; NF, neurofascin; NrCAM, neuronal CAM; shRNA, short hairpin RNA.
© 2008 Hedstrom et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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