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- Loss of -tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function
Loss of -tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function
Auteurs
K. Ikegami, R. L. Heier, M. Taruishi, H. Takagi, M. Mukai, S. Shimma, S. Taira, K. Hatanaka, N. Morone, I. Yao, P. K. Campbell, S. Yuasa, C. Janke, G. R. MacGregor, M. Setou
Résumé
Microtubules function as molecular tracks along which motor proteins transport a variety of cargo to discrete destinations within the cell. The carboxyl termini of α- and β-tubulin can undergo different posttranslational modifications, including polyglutamylation, which is particularly abundant within the mammalian nervous system. Thus, this modification could serve as a molecular “traffic sign” for motor proteins in neuronal cells. To investigate whether polyglutamylated α-tubulin could perform this function, we analyzed ROSA22 mice that lack functional PGs1, a subunit of α-tubulin-selective polyglutamylase. In wild-type mice, polyglutamylated α-tubulin is abundant in both axonal and dendritic neurites. ROSA22 mutants display a striking loss of polyglutamylated α-tubulin within neurons, including their neurites, which is associated with decreased binding affinity of certain structural microtubule-associated proteins and motor proteins, including kinesins, to microtubules purified from ROSA22-mutant brain. Of the kinesins examined, KIF1A, a subfamily of kinesin-3, was less abundant in neurites from ROSA22 mutants
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