Kalinski, AL;
Kar, AN;
Craver, J;
Tosolini, AP;
Sleigh, JN;
Lee, SJ;
Hawthorne, A;
... Twiss, JL; + view all
(2019)
Deacetylation of Miro1 by HDAC6 blocks mitochondrial transport and mediates axon growth inhibition.
Journal of Cell Biology
, 218
(6)
pp. 1871-1890.
10.1083/jcb.201702187.
Preview |
Text
jcb.201702187.full.pdf - Published Version Download (6MB) | Preview |
Abstract
Inhibition of histone deacetylase 6 (HDAC6) was shown to support axon growth on the nonpermissive substrates myelin-associated glycoprotein (MAG) and chondroitin sulfate proteoglycans (CSPGs). Though HDAC6 deacetylates α-tubulin, we find that another HDAC6 substrate contributes to this axon growth failure. HDAC6 is known to impact transport of mitochondria, and we show that mitochondria accumulate in distal axons after HDAC6 inhibition. Miro and Milton proteins link mitochondria to motor proteins for axon transport. Exposing neurons to MAG and CSPGs decreases acetylation of Miro1 on Lysine 105 (K105) and decreases axonal mitochondrial transport. HDAC6 inhibition increases acetylated Miro1 in axons, and acetyl-mimetic Miro1 K105Q prevents CSPG-dependent decreases in mitochondrial transport and axon growth. MAG- and CSPG-dependent deacetylation of Miro1 requires RhoA/ROCK activation and downstream intracellular Ca2+ increase, and Miro1 K105Q prevents the decrease in axonal mitochondria seen with activated RhoA and elevated Ca2+ These data point to HDAC6-dependent deacetylation of Miro1 as a mediator of axon growth inhibition through decreased mitochondrial transport.
| Type: | Article |
|---|---|
| Title: | Deacetylation of Miro1 by HDAC6 blocks mitochondrial transport and mediates axon growth inhibition |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1083/jcb.201702187 |
| Publisher version: | https://doi.org/10.1083/jcb.201702187 |
| Language: | English |
| Additional information: | Copyright © 2019 Kalinski 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.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
| Keywords: | Trafficking, Neuroscience, Cell Signaling |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10073584 |
Archive Staff Only
 |
View Item |
