RRC ID 65339
Author Chen YC, Huang HR, Hsu CH, Ou CY.
Title CRMP/UNC-33 organizes microtubule bundles for KIF5-mediated mitochondrial distribution to axon.
Journal PLoS Genet
Abstract Neurons are highly specialized cells with polarized cellular processes and subcellular domains. As vital organelles for neuronal functions, mitochondria are distributed by microtubule-based transport systems. Although the essential components of mitochondrial transport including motors and cargo adaptors are identified, it is less clear how mitochondrial distribution among somato-dendritic and axonal compartment is regulated. Here, we systematically study mitochondrial motors, including four kinesins, KIF5, KIF17, KIF1, KLP-6, and dynein, and transport regulators in C. elegans PVD neurons. Among all these motors, we found that mitochondrial export from soma to neurites is mainly mediated by KIF5/UNC-116. Interestingly, UNC-116 is especially important for axonal mitochondria, while dynein removes mitochondria from all plus-end dendrites and the axon. We surprisingly found one mitochondrial transport regulator for minus-end dendritic compartment, TRAK-1, and two mitochondrial transport regulators for axonal compartment, CRMP/UNC-33 and JIP3/UNC-16. While JIP3/UNC-16 suppresses axonal mitochondria, CRMP/UNC-33 is critical for axonal mitochondria; nearly no axonal mitochondria present in unc-33 mutants. We showed that UNC-33 is essential for organizing the population of UNC-116-associated microtubule bundles, which are tracks for mitochondrial trafficking. Disarrangement of these tracks impedes mitochondrial transport to the axon. In summary, we identified a compartment-specific transport regulation of mitochondria by UNC-33 through organizing microtubule tracks for different kinesin motors other than microtubule polarity.
Volume 17(2)
Pages e1009360
Published 2021-2-1
DOI 10.1371/journal.pgen.1009360
PII PGENETICS-D-20-01044
PMID 33571181
PMC PMC7904166
MeSH Animals Animals, Genetically Modified Axons / metabolism* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Dendrites / metabolism Dyneins / metabolism Kinesins / genetics Kinesins / metabolism* Microscopy, Confocal Microscopy, Fluorescence Microtubules / metabolism* Mitochondria / metabolism* Mutation Nerve Growth Factors / genetics Nerve Growth Factors / metabolism* Neurons / metabolism Protein Transport
Resource
C.elegans tm1966 tm1572