Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27710, USA.
J Biol Chem. 2010 Apr 9;285(15):11219-26. doi: 10.1074/jbc.M109.042754. Epub 2010 Feb 4.
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.
组蛋白去乙酰化酶 6（HDAC6）是一种微管相关去乙酰化酶，具有微管去乙酰化酶活性，并与动力蛋白结合。最近的研究表明，微管乙酰化会影响微管马达的亲和力和进程。这些独特的特性暗示 HDAC6 在细胞内细胞器运输中起作用。在这里，我们表明 HDAC6 与内体隔室相关联，并控制表皮生长因子受体（EGFR）的运输和降解。我们发现 HDAC6 的缺失会促进 EGFR 的降解。从机制上讲，HDAC6 的缺乏不会导致 EGFR 内化和回收异常。相反，它导致 EGFR 从早期内体中快速分离，并提前将 EGFR 运送到晚期内体和溶酶体隔室。失调的 EGFR 内吞运输伴随着携带 EGFR 的囊泡的微管依赖性运动增加，揭示了微管去乙酰化酶 HDAC6 对 EGFR 囊泡运输和降解的新调控。
