期刊
JOURNAL OF CELL BIOLOGY
卷 220, 期 12, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201905065
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资金
- National Health and Medical Research Council of Australia [APP1156489, APP1099251]
- National Health and Medical Research Council Emerging Leader Fellowship [1174145]
- Australian Research Council [DP200102559]
- Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology [CE140100036]
- Australian Research Council Centre of Excellence in Synthetic Biology [CE200100029]
- CSIRO- Queensland University of Technology Synthetic Biology Alliance
- Australian Cancer Research Foundation
- National Health and Medical Research Council of Australia [1174145] Funding Source: NHMRC
- Australian Research Council [DP200102559] Funding Source: Australian Research Council
Cavin4 plays a crucial role in remodeling the T-tubule membrane early in development by recycling caveolar components from the T-tubule to generate a stable T-tubule domain lacking caveolae, which is essential for T-tubule function.
The cavin proteins are essential for caveola biogenesis and function. Here, we identify a role for the muscle-specific component, Cavin4, in skeletal muscle T-tubule development by analyzing two vertebrate systems, mouse and zebrafish. In both models, Cavin4 localized to T-tubules, and loss of Cavin4 resulted in aberrant T-tubule maturation. In zebrafish, which possess duplicated cavin4 paralogs, Cavin4b was shown to directly interact with the T-tubule-associated BAR domain protein Bin1. Loss of both Cavin4a and Cavin4b caused aberrant accumulation of interconnected caveolae within the T-tubules, a fragmented T-tubule network enriched in Caveolin-3, and an impaired Ca2+ response upon mechanical stimulation. We propose a role for Cavin4 in remodeling the T-tubule membrane early in development by recycling caveolar components from the T-tubule to the sarcolemma. This generates a stable T-tubule domain lacking caveolae that is essential for T-tubule function.
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