Polarity of varicosity initiation in central neuron mechanosensation

Yuanzheng Gu, Peter Jukkola, Qian Wang, Thomas Esparza, Yi Zhao, David Brody, Chen Gu: 2017 Journal of Cell Biology Volume 216, Issue 7, Pages 2179-2199 Read More

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. © 2017 Gu et al.

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Posted on July 28, 2017
Posted in: Axon Injury & Repair, HPAN, Neurodegeneration, Neurogenetics & Transcriptomics, Neurovascular Injury & Repair, Publications Authors: