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TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays.

Authors :
van Beuningen SFB
Will L
Harterink M
Chazeau A
van Battum EY
Frias CP
Franker MAM
Katrukha EA
Stucchi R
Vocking K
Antunes AT
Slenders L
Doulkeridou S
Sillevis Smitt P
Altelaar AFM
Post JA
Akhmanova A
Pasterkamp RJ
Kapitein LC
de Graaff E
Hoogenraad CC
Source :
Neuron [Neuron] 2015 Dec 16; Vol. 88 (6), pp. 1208-1226. Date of Electronic Publication: 2015 Dec 06.
Publication Year :
2015

Abstract

Axon formation, the initial step in establishing neuronal polarity, critically depends on local microtubule reorganization and is characterized by the formation of parallel microtubule bundles. How uniform microtubule polarity is achieved during axonal development remains an outstanding question. Here, we show that the tripartite motif containing (TRIM) protein TRIM46 plays an instructive role in the initial polarization of neuronal cells. TRIM46 is specifically localized to the newly specified axon and, at later stages, partly overlaps with the axon initial segment (AIS). TRIM46 specifically forms closely spaced parallel microtubule bundles oriented with their plus-end out. Without TRIM46, all neurites have a dendrite-like mixed microtubule organization resulting in Tau missorting and altered cargo trafficking. By forming uniform microtubule bundles in the axon, TRIM46 is required for neuronal polarity and axon specification in vitro and in vivo. Thus, TRIM46 defines a unique axonal cytoskeletal compartment for regulating microtubule organization during neuronal development.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4199
Volume :
88
Issue :
6
Database :
MEDLINE
Journal :
Neuron
Publication Type :
Academic Journal
Accession number :
26671463
Full Text :
https://doi.org/10.1016/j.neuron.2015.11.012