NudC regulated Lis1 stability is essential for the maintenance of dynamic microtubule ends in axon terminals
Dane Kawano,
Katherine Pinter,
Madison Chlebowski,
Ronald S. Petralia,
Ya-Xian Wang,
Alex V. Nechiporuk,
Catherine M. Drerup
Affiliations
Dane Kawano
Unit on Neuronal Cell Biology, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892, USA
Katherine Pinter
Unit on Neuronal Cell Biology, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892, USA
Madison Chlebowski
Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI 53706, USA
Ronald S. Petralia
Advanced Imaging Core, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA
Ya-Xian Wang
Advanced Imaging Core, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA
Alex V. Nechiporuk
Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA
Catherine M. Drerup
Unit on Neuronal Cell Biology, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892, USA; Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI 53706, USA; Corresponding author
Summary: In the axon terminal, microtubule stability is decreased relative to the axon shaft. The dynamic microtubule plus ends found in the axon terminal have many functions, including serving as a docking site for the Cytoplasmic dynein motor. Here, we report an unexplored function of dynein in microtubule regulation in axon terminals: regulation of microtubule stability. Using a forward genetic screen, we identified a mutant with an abnormal axon terminal structure owing to a loss of function mutation in NudC. We show that, in the axon terminal, NudC is a chaperone for the protein Lis1. Decreased Lis1 in nudc axon terminals causes dynein/dynactin accumulation and increased microtubule stability. Microtubule dynamics can be restored by pharmacologically inhibiting dynein, implicating excess dynein motor function in microtubule stabilization. Together, our data support a model in which local NudC-Lis1 modulation of the dynein motor is critical for the regulation of microtubule stability in the axon terminal.
