Phosphorylation of Highly Conserved Neurofilament Medium KSP Repeats is Not Required for Myelin-dependent Radial Axonal Growth

Overview

Journal J Neurosci

Specialty Neurology

Date 2009 Feb 6

PMID 19193875

Citations 26

Authors

Michael L Garcia

Mala V Rao

Jiro Fujimoto

Virginia B Garcia

Sameer B Shah

John Crum

Takahiro Gotow

Yasuo Uchiyama

Mark Ellisman

Nigel A Calcutt

Don W Cleveland

Affiliations

Soon will be listed here.

Abstract

Neurofilament medium (NF-M) is essential for the acquisition of normal axonal caliber in response to a myelin-dependent "outside-in" trigger for radial axonal growth. Removal of the tail domain and lysine-serine-proline (KSP) repeats of NF-M, but not neurofilament heavy, produced axons with impaired radial growth and reduced conduction velocities. These earlier findings supported myelin-dependent phosphorylation of NF-M KSP repeats as an essential component of axonal growth. As a direct test of whether phosphorylation of NF-M KSP repeats is the target for the myelin-derived signal, gene replacement has now been used to produce mice in which all serines of NF-M's KSP repeats have been replaced with phosphorylation-incompetent alanines. This substitution did not alter accumulation of the neurofilaments or their subunits. Axonal caliber and motor neuron conduction velocity of mice expressing KSP phospho-incompetent NF-M were also indistinguishable from wild-type mice. Thus, phosphorylation of NF-M KSP repeats is not an essential component for the acquisition of normal axonal caliber mediated by myelin-dependent outside-in signaling.

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