Cavin4 Interacts with Bin1 to Promote T-tubule Formation and Stability in Developing Skeletal Muscle

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2021 Oct 11

PMID 34633413

Citations 14

Authors

Harriet P Lo

Ye-Wheen Lim

Zherui Xiong

Nick Martel

Charles Ferguson

Nicholas Ariotti

Jean Giacomotto

James Rae

Matthias Floetenmeyer

Shayli Varasteh Moradi

Ya Gao

Vikas A Tillu

Di Xia

Huang Wang

Samira Rahnama

Susan J Nixon

Michele Bastiani

Ryan D Day

Kelly A Smith

Nathan J Palpant

Wayne A Johnston

Kirill Alexandrov

Brett M Collins

Thomas E Hall

Robert G Parton

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Intracellular Membrane Contact Sites in Skeletal Muscle Cells.

Serano M, Perni S, Pierantozzi E, Laurino A, Sorrentino V, Rossi D Membranes (Basel). 2025; 15(1).

PMID: 39852269 PMC: 11767089. DOI: 10.3390/membranes15010029.

Unraveling calcium dysregulation and autoimmunity in immune mediated rippling muscle disease.

Nath S, Dasgupta A, Dubey D, Kokesh E, Beecher G, Fadra N Acta Neuropathol Commun. 2025; 13(1):11.

PMID: 39819455 PMC: 11736958. DOI: 10.1186/s40478-025-01926-z.

Genome-wide association study for growth traits with 1066 individuals in largemouth bass ().

Han W, Qi M, Ye K, He Q, Yekefenhazi D, Xu D Front Mol Biosci. 2024; 11:1443522.

PMID: 39385983 PMC: 11461307. DOI: 10.3389/fmolb.2024.1443522.

Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum.

Yang Y, Valencia L, Lu C, Nakamoto M, Tsai C, Liu C Nat Cell Biol. 2024; 26(11):1878-1891.

PMID: 39289582 PMC: 11567891. DOI: 10.1038/s41556-024-01511-x.

Uncovering the BIN1-SH3 interactome underpinning centronuclear myopathy.

Zambo B, Edelweiss E, Morlet B, Negroni L, Pajkos M, Dosztanyi Z Elife. 2024; 13.

PMID: 38995680 PMC: 11245310. DOI: 10.7554/eLife.95397.

References

Way M, Parton R . M-caveolin, a muscle-specific caveolin-related protein. FEBS Lett. 1995; 376(1-2):108-12. DOI: 10.1016/0014-5793(95)01256-7. View

Rae J, Ferguson C, Ariotti N, Webb R, Cheng H, Mead J . A robust method for particulate detection of a genetic tag for 3D electron microscopy. Elife. 2021; 10. PMC: 8104959. DOI: 10.7554/eLife.64630. View

Nixon S, Wegner J, Ferguson C, Mery P, Hancock J, Currie P . Zebrafish as a model for caveolin-associated muscle disease; caveolin-3 is required for myofibril organization and muscle cell patterning. Hum Mol Genet. 2005; 14(13):1727-43. DOI: 10.1093/hmg/ddi179. View

Richter T, Floetenmeyer M, Ferguson C, Galea J, Goh J, Lindsay M . High-resolution 3D quantitative analysis of caveolar ultrastructure and caveola-cytoskeleton interactions. Traffic. 2008; 9(6):893-909. DOI: 10.1111/j.1600-0854.2008.00733.x. View

Rodriguez G, Ueyama T, Ogata T, Czernuszewicz G, Tan Y, Dorn 2nd G . Molecular genetic and functional characterization implicate muscle-restricted coiled-coil gene (MURC) as a causal gene for familial dilated cardiomyopathy. Circ Cardiovasc Genet. 2011; 4(4):349-58. PMC: 3157556. DOI: 10.1161/CIRCGENETICS.111.959866. View

Lee J, Schmid-Schonbein G . Biomechanics of skeletal muscle capillaries: hemodynamic resistance, endothelial distensibility, and pseudopod formation. Ann Biomed Eng. 1995; 23(3):226-46. DOI: 10.1007/BF02584425. View

Smith L, Gupta V, Beggs A . Bridging integrator 1 (Bin1) deficiency in zebrafish results in centronuclear myopathy. Hum Mol Genet. 2014; 23(13):3566-78. PMC: 4049309. DOI: 10.1093/hmg/ddu067. View

McMahon K, Zajicek H, Li W, Peyton M, Minna J, Hernandez V . SRBC/cavin-3 is a caveolin adapter protein that regulates caveolae function. EMBO J. 2009; 28(8):1001-15. PMC: 2683698. DOI: 10.1038/emboj.2009.46. View

Ariotti N, Hall T, Rae J, Ferguson C, McMahon K, Martel N . Modular Detection of GFP-Labeled Proteins for Rapid Screening by Electron Microscopy in Cells and Organisms. Dev Cell. 2015; 35(4):513-25. DOI: 10.1016/j.devcel.2015.10.016. View

10.

Lee E, Marcucci M, Daniell L, Pypaert M, Weisz O, Farsad K . Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle. Science. 2002; 297(5584):1193-6. DOI: 10.1126/science.1071362. View

11.

Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B . Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science. 2001; 293(5539):2449-52. DOI: 10.1126/science.1062688. View

12.

Dulhunty A, Franzini-Armstrong C . The relative contributions of the folds and caveolae to the surface membrane of frog skeletal muscle fibres at different sarcomere lengths. J Physiol. 1975; 250(3):513-39. PMC: 1348391. DOI: 10.1113/jphysiol.1975.sp011068. View

13.

Franzini-Armstrong C, Landmesser L, PILAR G . Size and shape of transverse tubule openings in frog twitch muscle fibers. J Cell Biol. 1975; 64(2):493-7. PMC: 2109503. DOI: 10.1083/jcb.64.2.493. View

14.

Smith K, Lagendijk A, Courtney A, Chen H, Paterson S, Hogan B . Transmembrane protein 2 (Tmem2) is required to regionally restrict atrioventricular canal boundary and endocardial cushion development. Development. 2011; 138(19):4193-8. DOI: 10.1242/dev.065375. View

15.

Wienholds E, van Eeden F, Kosters M, Mudde J, Plasterk R, Cuppen E . Efficient target-selected mutagenesis in zebrafish. Genome Res. 2003; 13(12):2700-7. PMC: 403812. DOI: 10.1101/gr.1725103. View

16.

Balijepalli R, Kamp T . Caveolae, ion channels and cardiac arrhythmias. Prog Biophys Mol Biol. 2009; 98(2-3):149-60. PMC: 2836876. DOI: 10.1016/j.pbiomolbio.2009.01.012. View

17.

Hohendahl A, Roux A, Galli V . Structural insights into the centronuclear myopathy-associated functions of BIN1 and dynamin 2. J Struct Biol. 2016; 196(1):37-47. PMC: 5039012. DOI: 10.1016/j.jsb.2016.06.015. View

18.

Carozzi A, Ikonen E, Lindsay M, Parton R . Role of cholesterol in developing T-tubules: analogous mechanisms for T-tubule and caveolae biogenesis. Traffic. 2001; 1(4):326-41. DOI: 10.1034/j.1600-0854.2000.010406.x. View

19.

Flucher B . Structural analysis of muscle development: transverse tubules, sarcoplasmic reticulum, and the triad. Dev Biol. 1992; 154(2):245-60. DOI: 10.1016/0012-1606(92)90065-o. View

20.

Ibrahim M, Gorelik J, Yacoub M, Terracciano C . The structure and function of cardiac t-tubules in health and disease. Proc Biol Sci. 2011; 278(1719):2714-23. PMC: 3145195. DOI: 10.1098/rspb.2011.0624. View