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Excessive mechanotransduction in sensory neurons causes joint contractures
In: Science, Jg. 379 (2023-01-13), Heft 6628, S. 201-206
Online
academicJournal
Zugriff:
Distal arthrogryposis (DA) is a collection of rare disorders that are characterized by congenital joint contractures. Most DA mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal system. However, gain-of-function mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 (DA5) through unknown mechanisms. We show that expression of a gain-of-function PIEZO2 mutation in proprioceptive sensory neurons that mainly innervate muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects through increased activity within the peripheral nervous system during postnatal development. Furthermore, botulinum toxin (Botox) and a dietary fatty acid that modulates PIEZO2 activity reduce DA5-like deficits. This reveals a role for somatosensory neurons: Excessive mechanosensation within these neurons disrupts musculoskeletal development.
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Excessive mechanotransduction in sensory neurons causes joint contractures
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Autor/in / Beteiligte Person: | Ma, Shang ; Dubin, Adrienne E. ; Romero, Luis O. ; Loud, Meaghan ; Salazar, Alexandra ; Chu, Sarah ; Klier, Nikola ; Masri, Sameer ; Zhang, Yunxiao ; Wang, Yu ; Chester, Alex T. ; Wilkinson, Katherine A. ; Vasquez, Valeria ; Marshall, Kara L. ; Patapoutian, Ardem |
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Zeitschrift: | Science, Jg. 379 (2023-01-13), Heft 6628, S. 201-206 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 0036-8075 (print) |
DOI: | 10.1126/science.add3598 |
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