Cell Biology
The Microtubule-associated Histone Deacetylase 6 (HDAC6) Regulates Epidermal Growth Factor Receptor (EGFR) Endocytic Trafficking and Degradation*

https://doi.org/10.1074/jbc.M109.042754Get rights and content
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Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase with tubulin deacetylase activity, and it binds dynein motors. Recent studies revealed that microtubule acetylation affects the affinity and processivity of microtubule motors. These unique properties implicate a role for HDAC6 in intracellular organelle transport. Here, we show that HDAC6 associates with the endosomal compartments and controls epidermal growth factor receptor (EGFR) trafficking and degradation. We found that loss of HDAC6 promoted EGFR degradation. Mechanistically, HDAC6 deficiency did not cause aberrant EGFR internalization and recycling. Rather, it resulted in accelerated segregation of EGFR from early endosomes and premature delivery of EGFR to the late endosomal and lysosomal compartments. The deregulated EGFR endocytic trafficking was accompanied by an increase in microtubule-dependent movement of EGFR-bearing vesicles, revealing a novel regulation of EGFR vesicular trafficking and degradation by the microtubule deacetylase HDAC6.

Cytoskeleton/Microtubules
Histones/Deacetylase
Protein/Intracellular Trafficking
Receptors
Subcellular Organelles/Endosomes
EGFR degradation
HDAC6
Tubulin Acetylation

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*

This work was supported in part, by National Institutes of Health Grant NS053825. This work was also supported by Department of Defense Grants PC 050119 (to Y.-s. G.) and DAMD 17-01-1-0054 and the Leukemia and Lymphoma Society (to T.-P. Y.).