CRMP/UNC-33 organizes microtubule bundles for KIF5-mediated mitochondrial distribution to axon

English version

Autoři: Ying-Chun Chen ^aff001; Hao-Ru Huang ^aff001; Chia-Hao Hsu ^aff001; Chan-Yen Ou ^aff001
Působiště autorů: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan ^aff001
Vyšlo v časopise: CRMP/UNC-33 organizes microtubule bundles for KIF5-mediated mitochondrial distribution to axon. PLoS Genet 17(2): e1009360. doi:10.1371/journal.pgen.1009360
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009360

Souhrn

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.

Klíčová slova:

Mitochondria – Axonal transport – Axons – Microtubules – Motor neurons – Neurites – Neuronal dendrites – Neurons

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