Optogenetic manipulation of cellular communication using engineered myosin motors

Nat Cell Biol. 2021 Feb;23(2):198-208. doi: 10.1038/s41556-020-00625-2. Epub 2021 Feb 1.


Cells achieve highly efficient and accurate communication through cellular projections such as neurites and filopodia, yet there is a lack of genetically encoded tools that can selectively manipulate their composition and dynamics. Here, we present a versatile optogenetic toolbox of artificial multi-headed myosin motors that can move bidirectionally within long cellular extensions and allow for the selective transport of GFP-tagged cargo with light. Utilizing these engineered motors, we could transport bulky transmembrane receptors and organelles as well as actin remodellers to control the dynamics of both filopodia and neurites. Using an optimized in vivo imaging scheme, we further demonstrate that, upon limb amputation in axolotls, a complex array of filopodial extensions is formed. We selectively modulated these filopodial extensions and showed that they re-establish a Sonic Hedgehog signalling gradient during regeneration. Considering the ubiquitous existence of actin-based extensions, this toolbox shows the potential to manipulate cellular communication with unprecedented accuracy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Ambystoma mexicanum / physiology
  • Animals
  • Biological Transport
  • Cell Communication*
  • Cell Line
  • Cell Survival / radiation effects
  • Extremities / physiology
  • Green Fluorescent Proteins / metabolism
  • Hedgehog Proteins / metabolism
  • Kinetics
  • Light
  • Mice
  • Mouse Embryonic Stem Cells / metabolism
  • Myosins / metabolism*
  • Neurites / metabolism
  • Optogenetics*
  • Protein Engineering*
  • Pseudopodia / metabolism
  • Regeneration / physiology
  • Signal Transduction
  • Transport Vesicles / metabolism


  • Hedgehog Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Myosins