PUBLICATION

NudC regulated Lis1 stability is essential for the maintenance of dynamic microtubule ends in axon terminals

Authors
Kawano, D., Pinter, K., Chlebowski, M., Petralia, R.S., Wang, Y.X., Nechiporuk, A.V., Drerup, C.M.
ID
ZDB-PUB-240603-10
Date
2022
Source
iScience   25: 105072105072 (Journal)
Registered Authors
Chlebowski, Mady, Drerup, Katie (Catherine), Nechiporuk, Alex, Pinter, Katherine
Keywords
Molecular neuroscience, developmental neuroscience, functional aspects of cell biology
MeSH Terms
none
PubMed
36147950 Full text @ iScience
Abstract
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.
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