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Open Access Research article

Hook2 contributes to aggresome formation

Györgyi Szebenyi1, W Christian Wigley23, Branden Hall1, Aaron Didier1, Michelle Yu1, Philip Thomas2 and Helmut Krämer1*

Author Affiliations

1 Center for Basic Neuroscience, University of Texas, Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, Texas 75390-9111, USA

2 Department of Physiology, University of Texas, Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, Texas 75390-9040, USA

3 Reata Pharmaceuticals, Inc., 2801 Gateway Drive, Irving TX 75063-2648, USA

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BMC Cell Biology 2007, 8:19  doi:10.1186/1471-2121-8-19

Published: 31 May 2007

Abstract

Background

Aggresomes are pericentrosomal accumulations of misfolded proteins, chaperones and proteasomes. Their positioning near the centrosome, like that of other organelles, requires active, microtubule-dependent transport. Linker proteins that can associate with the motor protein dynein, organelles, and microtubules are thought to contribute to the active maintenance of the juxtanuclear localization of many membrane bound organelles and aggresomes. Hook proteins have been proposed to serve as adaptors for the association of cargos with dynein for transport on microtubules. Hook2 was shown to localize to the centrosome, bind centriolin, and contribute to centrosomal function.

Results

Here we show that overexpression of hook2 promotes the accumulation of the cystic fibrosis transmembrane regulator in aggresomes without altering its biochemical properties or its steady state level. A dominant negatively acting form of hook2 that lacks the centriolin binding C-terminal inhibits aggresome formation.

Conclusion

We propose that hook2 contributes to the establishment and maintenance of the pericentrosomal localization of aggresomes by promoting the microtubule-based delivery of protein aggregates to pericentriolar aggresomes.