Establishing neuronal polarity: microtubule regulation during neurite initiation

Higgs, Victoria E; Das, Raman M

doi:10.1093/oons/kvac007

Cited by 2 publications

(1 citation statement)

References 229 publications

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“…Neuronal polarization commences with axon specification (Dotti et al, 1988;Higgs and Das, 2022) determined by microtubule stabilization and bundling (Witte et al, 2008;Van Beuningen et al, 2015). Stability of the microtubules imparts strength to the growing axon, provides platform for other cytoskeletal interactions, promotes selective trafficking of molecules, and generate force for changes in morphology during growth (Hawkins et al, 2010;Kapitein and Hoogenraad, 2011).…”

Section: Klp-7/kinesin-13 Dependent Microtubule Organization Regulate...mentioning

confidence: 99%

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

Dey,

Kumar,

Feldman

et al. 2023

Preprint

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Neurons are compartmentalized cells with spatiotemporal distinction of anatomy and molecular repertoire. Microtubule organization in the neuron is crucial for its polarized structure and composition. Microtubule dynamics are differentially optimized in the axons and dendrites by the interplay between the microtubule-stabilizing and destabilizing factors. It is unclear how the destabilizing factors are important for developing and maintaining neuronal polarity. We investigated the function of KLP-7, a microtubule depolymerizing motor from the Kinesin-13 family, in the compartmentalization of axons and dendrites using the PVD neurons in Caenorhabditis elegans. In the absence of KLP-7, axonal proteins such as RAB-3 and SAD-1 were mislocalized to dendrites, suggesting a disruption in axon-dendrite compartmentalization. Notably, this phenomenon was independent of other depolymerizing factors like EFA-6, highlighting the specific role of KLP-7 in this process. We observed a reduced rate of microtubule polymerization and an altered polarity of microtubules in the PVD major dendrite due to the loss of klp-7. Additionally, the deletion of klp-7 led to the formation of ectopic neurites from the cell body and the ectopic localization of UNC-44/Ankyrin-G, a protein associated with the axon initial segment (AIS), to the dendrites. Additionally, live imaging of GFP::KLP-7 revealed that KLP-7 is more dynamic in the dendrites as compared to the axon. These observations indicate that the precise dynamics of KLP-7 in neurites are crucial for maintaining distinct microtubule polymerization in the axons and dendrites, thereby influencing neuronal polarity. Our findings shed light on the pivotal role of KLP-7/Kinesin-13 in the establishment of axon-dendrite checkpoints, which in turn impact the polarized trafficking of cellular components within neurons.

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Section: Klp-7/kinesin-13 Dependent Microtubule Organization Regulate...mentioning

confidence: 99%

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

Dey,

Kumar,

Feldman

et al. 2023

Preprint

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

Dey,

Kumar,

Balakrishnan

et al. 2024

MBoC

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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. 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 includes 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. [Media: see text] [Media: see text]

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Establishing neuronal polarity: microtubule regulation during neurite initiation

Cited by 2 publications

References 229 publications

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

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

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

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