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J Cell Sci. 2014 Sep 15;127(Pt 18):4052-63. doi: 10.1242/jcs.152363. Epub 2014 Jul 11.

Interaction of SQSTM1 with the motor protein dynein--SQSTM1 is required for normal dynein function and trafficking.

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  • 1Department of Biological Sciences, 331 Funchess Hall, Auburn University, Auburn, AL 36849, USA.
  • 210901 North Torrey Pines Road, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
  • 3Graduate Center for Toxicology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
  • 4Department of Biological Sciences, 331 Funchess Hall, Auburn University, Auburn, AL 36849, USA wootemc@auburn.edu.

Abstract

The dynein motor protein complex is required for retrograde transport of vesicular cargo and for transport of aggregated proteins along microtubules for processing and degradation at perinuclear aggresomes. Disruption of this process leads to dysfunctional endosome accumulation and increased protein aggregation in the cell cytoplasm, both pathological features of neurodegenerative diseases. However, the exact mechanism of dynein functionality in these pathways is still being elucidated. Here, we show that the scaffolding protein SQSTM1 directly interacts with dynein through a previously unidentified dynein-binding site. This interaction is independent of HDAC6, a known interacting protein of both SQSTM1 and dynein. However, knockdown of HDAC6 increases the interaction of SQSTM1 with dynein, indicating a possible competitive interaction. Using different dynein cargoes, we show that SQSTM1 is required for proper dynein motility and trafficking along microtubules. Based on our results, we propose a new model of competitive interaction between SQSTM1 and HDAC6 with dynein. In this model, SQSTM1 would not only affect the association of polyubiquitylated protein aggregates and endosomes with dynein, but would also be required for normal dynein function.

© 2014. Published by The Company of Biologists Ltd.

KEYWORDS:

Aggresome; Dynein intermediate chain; HDAC6; Histone deacetylase 6; Late endosome; SQSTM1

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