HDAC6 regulates microtubule stability and clustering of AChRs at neuromuscular junctions.

The Journal of Cell Biology
Alexis OsseniBernard J Jasmin

Abstract

Microtubules (MTs) are known to be post-translationally modified at the neuromuscular junction (NMJ), hence increasing their stability. To date however, the function(s) of the dynamic MT network and its relative stability in the formation and maintenance of NMJs remain poorly described. Stabilization of the MT is dependent in part on its acetylation status, and HDAC6 is capable of reversing this post-translational modification. Here, we report that HDAC6 preferentially accumulates at NMJs and that it contributes to the organization and the stability of NMJs. Indeed, pharmacological inhibition of HDAC6 protects against MT disorganization and reduces the size of acetylcholine receptor (AChR) clusters. Moreover, the endogenous HDAC6 inhibitor paxillin interacts with HDAC6 in skeletal muscle cells, colocalizes with AChR aggregates, and regulates the formation of AChR. Our findings indicate that the focal insertion of AChRs into the postsynaptic membrane is regulated by stable MTs and highlight how an MT/HDAC6/paxillin axis participates in the regulation of AChR insertion and removal to control the structure of NMJs.

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Datasets Mentioned

BETA
RMM3981-201801357

Methods Mentioned

BETA
acetylation
ubiquitination
fluorescence microscopy
co-immunoprecipitation
immunoprecipitation
coimmunoprecipitation
proximity ligation assay
transfection
transfections
PCR

Software Mentioned

GraphPad
Photoshop
ImageJ
Noldus
Zeiss AxioVision
FIJI
Prism
DigiGait
ZEN blue
Image

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