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

PLoS Genet. 2021 Feb 11;17(2):e1009360. doi: 10.1371/journal.pgen.1009360. eCollection 2021 Feb.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Nerve Growth Factors
  • UNC-116 protein, C elegans
  • unc-33 protein, C elegans
  • Dyneins
  • Kinesins