Nature Communications (May 2020)
TRPV4 disrupts mitochondrial transport and causes axonal degeneration via a CaMKII-dependent elevation of intracellular Ca2+
- Brian M. Woolums,
- Brett A. McCray,
- Hyun Sung,
- Masashi Tabuchi,
- Jeremy M. Sullivan,
- Kendra Takle Ruppell,
- Yunpeng Yang,
- Catherine Mamah,
- William H. Aisenberg,
- Pamela C. Saavedra-Rivera,
- Bryan S. Larin,
- Alexander R. Lau,
- Douglas N. Robinson,
- Yang Xiang,
- Mark N. Wu,
- Charlotte J. Sumner,
- Thomas E. Lloyd
Affiliations
- Brian M. Woolums
- Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine
- Brett A. McCray
- Department of Neurology, Johns Hopkins University School of Medicine
- Hyun Sung
- Department of Neurology, Johns Hopkins University School of Medicine
- Masashi Tabuchi
- Department of Neurology, Johns Hopkins University School of Medicine
- Jeremy M. Sullivan
- Department of Neurology, Johns Hopkins University School of Medicine
- Kendra Takle Ruppell
- Neurobiology Department, UMass Medical School
- Yunpeng Yang
- Department of Neurology, Johns Hopkins University School of Medicine
- Catherine Mamah
- Department of Neurology, Johns Hopkins University School of Medicine
- William H. Aisenberg
- Department of Neurology, Johns Hopkins University School of Medicine
- Pamela C. Saavedra-Rivera
- Department of Neurology, Johns Hopkins University School of Medicine
- Bryan S. Larin
- Department of Neurology, Johns Hopkins University School of Medicine
- Alexander R. Lau
- Department of Neurology, Johns Hopkins University School of Medicine
- Douglas N. Robinson
- Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine
- Yang Xiang
- Neurobiology Department, UMass Medical School
- Mark N. Wu
- Department of Neurology, Johns Hopkins University School of Medicine
- Charlotte J. Sumner
- Department of Neurology, Johns Hopkins University School of Medicine
- Thomas E. Lloyd
- Department of Neurology, Johns Hopkins University School of Medicine
- DOI
- https://doi.org/10.1038/s41467-020-16411-5
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 17
Abstract
Mutations in the TRPV4 channel cause inherited neurodegeneration syndromes, but the molecular mechanisms are unknown. Here the authors reveal that TRPV4 activation causes dose-dependent, CaMKII-mediated neuronal dysfunction and axonal degeneration via disruption of mitochondrial axonal transport.
