Regulation of MT dynamics via direct binding of an Abl family kinase

Author:

Hu Yuhan1ORCID,Lyu Wanqing2,Lowery Laura Anne3,Koleske Anthony J.24ORCID

Affiliation:

1. Department of Cell Biology, Yale University, New Haven, CT

2. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT

3. Department of Biology, Boston College, Chestnut Hill, MA

4. Department of Neuroscience, Yale University, New Haven, CT

Abstract

Abl family kinases are essential regulators of cell shape and movement. Genetic studies revealed functional interactions between Abl kinases and microtubules (MTs), but the mechanism by which Abl family kinases regulate MTs remains unclear. Here, we report that Abl2 directly binds to MTs and regulates MT behaviors. Abl2 uses its C-terminal half to bind MTs, an interaction mediated in part through electrostatic binding to tubulin C-terminal tails. Using purified proteins, we found that Abl2 binds growing MTs and promotes MT polymerization and stability. In cells, knockout of Abl2 significantly impairs MT growth, and this defect can be rescued via reexpression of Abl2. Stable reexpression of an Abl2 fragment containing the MT-binding domain alone was sufficient to restore MT growth at the cell edge. These results show Abl2 uses its C-terminal half to bind MTs and directly regulate MT dynamics.

Funder

National Institute of Neurological Disorders and Stroke

Randall W. Reyer Scholarship Fund

American Heart Association

National Institute of Mental Health

Publisher

Rockefeller University Press

Subject

Cell Biology

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