KLP-7/Kinesin-13 orchestrates axon-dendrite checkpoints for polarized trafficking in neurons.

Autor:	Dey S; Cellular and Molecular Neuroscience, National Brain Research Centre, Manesar, Gurugram, Haryana 122052, India., Kumar N; Cellular and Molecular Neuroscience, National Brain Research Centre, Manesar, Gurugram, Haryana 122052, India., Balakrishnan S; Cellular and Molecular Neuroscience, National Brain Research Centre, Manesar, Gurugram, Haryana 122052, India., Koushika SP; Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra 400005, India., Ghosh-Roy A; Cellular and Molecular Neuroscience, National Brain Research Centre, Manesar, Gurugram, Haryana 122052, India.
Jazyk:	angličtina
Zdroj:	Molecular biology of the cell [Mol Biol Cell] 2024 Sep 01; Vol. 35 (9), pp. ar115. Date of Electronic Publication: 2024 Jul 10.
DOI:	10.1091/mbc.E23-08-0335
Abstrakt:	The polarized nature of neurons depends on their microtubule dynamics and orientation determined by both microtubule-stabilizing and destabilizing factors. The role of destabilizing factors in developing and maintaining neuronal polarity is unclear. We investigated the function of KLP-7, a microtubule depolymerizing motor of the Kinesin-13 family, in axon-dendrite compartmentalization using PVD neurons in Caenorhabditis elegans . Loss of KLP-7 caused a mislocalization of axonal proteins, including RAB-3, SAD-1, and their motor UNC-104, to dendrites. This is rescued by cell-autonomous expression of the KLP-7 or colchicine treatment, indicating the involvement of KLP-7-dependent microtubule depolymerization. The high mobility of KLP-7 is correlated to increased microtubule dynamics in the dendrites, which restricts the enrichment of UNC-44, an integral component of Axon Initial Segment (AIS) in these processes. Due to the loss of KLP-7, ectopic enrichment of UNC-44 in the dendrite potentially redirects axonal traffic into dendrites that include plus-end out microtubules, axonal motors, and cargoes. These observations indicate that KLP-7-mediated depolymerization defines the microtubule dynamics conducive to the specific enrichment of AIS components in dendrites. This further compartmentalizes dendritic and axonal microtubules, motors, and cargoes, thereby influencing neuronal polarity. Competing Interests: Conflict of interests: The authors declare no competing financial interests.
Databáze:	MEDLINE
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