Myosin-Va transports the endoplasmic reticulum into the dendritic spines of Purkinje neurons

Nat Cell Biol. 2011 Jan;13(1):40-8. doi: 10.1038/ncb2132. Epub 2010 Dec 12.

Abstract

Extension of the endoplasmic reticulum (ER) into dendritic spines of Purkinje neurons is required for cerebellar synaptic plasticity and is disrupted in animals with null mutations in Myo5a, the gene encoding myosin-Va. We show here that myosin-Va acts as a point-to-point organelle transporter to pull ER as cargo into Purkinje neuron spines. Specifically, myosin-Va accumulates at the ER tip as the organelle moves into spines, and hydrolysis of ATP by myosin-Va is required for spine ER targeting. Moreover, myosin-Va is responsible for almost all of the spine ER insertion events. Finally, attenuation of the ability of myosin-Va to move along actin filaments reduces the maximum velocity of ER movement into spines, providing direct evidence that myosin-Va drives ER motility. Thus, we have established that an actin-based motor moves ER within animal cells, and have uncovered the mechanism for ER localization to Purkinje neuron spines, a prerequisite for synaptic plasticity.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Biological Transport
  • Calcium / metabolism
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Dendritic Spines / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Female
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Guanylate Kinases
  • Hydrolysis
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kinetics
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Microtubules / metabolism
  • Models, Neurological
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism*
  • Myosin Type V / genetics
  • Myosin Type V / metabolism*
  • Purkinje Cells / metabolism*
  • Receptors, AMPA / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Myo5a protein, mouse
  • Receptors, AMPA
  • Green Fluorescent Proteins
  • Adenosine Triphosphate
  • Dlgh2 protein, mouse
  • Guanylate Kinases
  • Myosin Type V
  • Myosin Heavy Chains
  • Calcium