Distinct functions of nuclear distribution proteins LIS1, Ndel1 and NudCL in regulating axonal mitochondrial transport

Traffic. 2013 Jul;14(7):785-97. doi: 10.1111/tra.12070. Epub 2013 Apr 22.

Abstract

Neurons critically depend on the long-distance transport of mitochondria. Motor proteins kinesin and dynein control anterograde and retrograde mitochondrial transport, respectively in axons. The regulatory molecules that link them to mitochondria need to be better characterized. Nuclear distribution (Nud) family proteins LIS1, Ndel1 and NudCL are critical components of cytoplasmic dynein complex. Roles of these Nud proteins in neuronal mitochondrial transport are unknown. Here we report distinct functions of LIS1, Ndel1 and NudCL on axonal mitochondrial transport in cultured hippocampal neurons. We found that LIS1 interacted with kinsein family protein KIF5b. Depletion of LIS1 enormously suppressed mitochondrial motility in both anterograde and retrograde directions. Inhibition of either Ndel1 or NudCL only partially reduced retrograde mitochondrial motility. However, knocking down both Ndel1 and NudCL almost blocked retrograde mitochondrial transport, suggesting these proteins may work together to regulate retrograde mitochondrial transport through linking dynein-LIS1 complex. Taken together, our results uncover novel roles of LIS1, Ndel1 and NudCL in the transport of mitochondria in axons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport*
  • Axons / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Gene Deletion
  • Hippocampus / cytology
  • Intracellular Signaling Peptides and Proteins
  • Kinesin / metabolism
  • Mitochondria / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • KIF5B protein, rat
  • Nerve Tissue Proteins
  • NudCL protein, rat
  • Pafah1b1 protein, rat
  • Cysteine Endopeptidases
  • Ndel1 protein, rat
  • Kinesin