Development and application of in vivo molecular traps reveals that dynein light chain occupancy differentially affects dynein-mediated processes.

Proceedings of the National Academy of Sciences of the United States of America
Dileep VarmaJohn C Williams

Abstract

The ability to rapidly and specifically regulate protein activity combined with in vivo functional assays and/or imaging can provide unique insight into underlying molecular processes. Here we describe the application of chemically induced dimerization of FKBP to create nearly instantaneous high-affinity bivalent ligands capable of sequestering cellular targets from their endogenous partners. We demonstrate the specificity and efficacy of these inducible, dimeric "traps" for the dynein light chains LC8 (Dynll1) and TcTex1 (Dynlt1). Both light chains can simultaneously bind at adjacent sites of dynein intermediate chain at the base of the dynein motor complex, yet their specific function with respect to the dynein motor or other interacting proteins has been difficult to dissect. Using these traps in cultured mammalian cells, we observed that induction of dimerization of either the LC8 or TcTex1 trap rapidly disrupted early endosomal and lysosomal organization. Dimerization of either trap also disrupted Golgi organization, but at a substantially slower rate. Using either trap, the time course for disruption of each organelle was similar, suggesting a common regulatory mechanism. However, despite the essential role of dynein in c...Continue Reading

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Citations

Oct 5, 2010·The Journal of Biological Chemistry·László RadnaiLászló Nyitray
Oct 6, 2012·The Journal of Biological Chemistry·Jayant AsthanaDulal Panda
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Jun 19, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jian ChenGuo-Yong Yin
Jun 14, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shoko EdogawaMadhusudan Grover
Jan 15, 2014·The Journal of Biological Chemistry·Shubbir AhmedJohn C Williams
Jan 15, 2021·Journal of the American Society of Nephrology : JASN·Hua SunMartin R Pollak

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