Optogenetic control of organelle transport and positioning

Nature. 2015 Feb 5;518(7537):111-114. doi: 10.1038/nature14128. Epub 2015 Jan 7.

Abstract

Proper positioning of organelles by cytoskeleton-based motor proteins underlies cellular events such as signalling, polarization and growth. For many organelles, however, the precise connection between position and function has remained unclear, because strategies to control intracellular organelle positioning with spatiotemporal precision are lacking. Here we establish optical control of intracellular transport by using light-sensitive heterodimerization to recruit specific cytoskeletal motor proteins (kinesin, dynein or myosin) to selected cargoes. We demonstrate that the motility of peroxisomes, recycling endosomes and mitochondria can be locally and repeatedly induced or stopped, allowing rapid organelle repositioning. We applied this approach in primary rat hippocampal neurons to test how local positioning of recycling endosomes contributes to axon outgrowth and found that dynein-driven removal of endosomes from axonal growth cones reversibly suppressed axon growth, whereas kinesin-driven endosome enrichment enhanced growth. Our strategy for optogenetic control of organelle positioning will be widely applicable to explore site-specific organelle functions in different model systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Axons / radiation effects
  • Biological Transport / radiation effects
  • Cell Compartmentation / physiology*
  • Cell Compartmentation / radiation effects
  • Cells, Cultured
  • Cytoskeleton / metabolism
  • Cytoskeleton / radiation effects
  • Dendritic Spines / metabolism
  • Dendritic Spines / radiation effects
  • Dyneins / metabolism
  • Dyneins / radiation effects
  • Endosomes / metabolism*
  • Endosomes / radiation effects
  • Hippocampus / cytology
  • Intracellular Space / metabolism
  • Intracellular Space / radiation effects
  • Kinesin / metabolism
  • Kinesin / radiation effects
  • Microtubules / metabolism
  • Microtubules / radiation effects
  • Mitochondria / metabolism*
  • Mitochondria / radiation effects
  • Myosin Type V / metabolism
  • Myosin Type V / radiation effects
  • Optogenetics / methods*
  • Peroxisomes / metabolism*
  • Peroxisomes / radiation effects
  • Rats

Substances

  • Myosin Type V
  • Dyneins
  • Kinesin