TY - JOUR
T1 - NudC regulated Lis1 stability is essential for the maintenance of dynamic microtubule ends in axon terminals
AU - Kawano, Dane
AU - Pinter, Katherine
AU - Chlebowski, Madison
AU - Petralia, Ronald S.
AU - Wang, Ya Xian
AU - Nechiporuk, Alex V.
AU - Drerup, Catherine M.
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/10/21
Y1 - 2022/10/21
N2 - 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.
AB - 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.
KW - Molecular neuroscience
KW - developmental neuroscience
KW - functional aspects of cell biology
UR - http://www.scopus.com/inward/record.url?scp=85138116209&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138116209&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.105072
DO - 10.1016/j.isci.2022.105072
M3 - Article
AN - SCOPUS:85138116209
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 10
M1 - 105072
ER -