Polarity of varicosity initiation in central neuron mechanosensation

J Cell Biol. 2017 Jul 3;216(7):2179-2199. doi: 10.1083/jcb.201606065. Epub 2017 Jun 12.

Abstract

Little is known about mechanical regulation of morphological and functional polarity of central neurons. In this study, we report that mechanical stress specifically induces varicosities in the axons but not the dendrites of central neurons by activating TRPV4, a Ca2+/Na+-permeable mechanosensitive channel. This process is unexpectedly rapid and reversible, consistent with the formation of axonal varicosities in vivo induced by mechanical impact in a mouse model of mild traumatic brain injury. In contrast, prolonged stimulation of glutamate receptors induces varicosities in dendrites but not in axons. We further show that axonal varicosities are induced by persistent Ca2+ increase, disassembled microtubules (MTs), and subsequently reversible disruption of axonal transport, and are regulated by stable tubulin-only polypeptide, an MT-associated protein. Finally, axonal varicosity initiation can trigger action potentials to antidromically propagate to the soma in retrograde signaling. Therefore, our study demonstrates a new feature of neuronal polarity: axons and dendrites preferentially respond to physical and chemical stresses, respectively.

Publication types

  • Video-Audio Media
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials
  • Animals
  • Axons / metabolism
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / physiopathology
  • Calcium Signaling
  • Cell Polarity*
  • Dendrites / metabolism
  • Disease Models, Animal
  • HEK293 Cells
  • Hippocampus / embryology
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Male
  • Mechanotransduction, Cellular*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubules / metabolism
  • Neuronal Plasticity
  • Neurons / metabolism*
  • Neurons / pathology
  • Physical Stimulation
  • RNA Interference
  • Rats
  • Receptors, Glutamate / metabolism
  • Stress, Mechanical
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Time Factors
  • Transfection

Substances

  • Receptors, Glutamate
  • TRPV Cation Channels
  • TRPV4 protein, human
  • Trpv4 protein, mouse
  • Trpv4 protein, rat

Associated data

  • GENBANK/NM_023970