Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle

2021 ◽  
Vol 220 (12) ◽  
Author(s):  
Harriet P. Lo ◽  
Ye-Wheen Lim ◽  
Zherui Xiong ◽  
Nick Martel ◽  
Charles Ferguson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mechanical Stimulation ◽  
Specific Component ◽  
Tubule Formation ◽  
Bar Domain ◽  
T Tubules ◽  
Domain Protein ◽  
And 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.

scholarly journals Muscle-specific Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle

2021 ◽  
Author(s):  
Harriet P. Lo ◽  
Ye-Wheen Lim ◽  
Zherui Xiong ◽  
Nick Martel ◽  
Charles Ferguson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mechanical Stimulation ◽  
Specific Component ◽  
Tubule Formation ◽  
Bar Domain ◽  
T Tubules ◽  
Domain Protein ◽  
And Function

SummaryThe 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.

scholarly journals Bin1, A Bar Domain Protein, Is Necessary For The Maintenance Of T-tubule Structure And Intracellular Ca2+ Homeostasis In Skeletal Muscle

2009 ◽  
Vol 96 (3) ◽  
pp. 280a
Author(s):  
Andoria Tjondrokoesoemo ◽  
Shinji Komazaki ◽  
Christopher Ferrante ◽  
Jingsong Zhou ◽  
Jianjie Ma ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bar Domain ◽  
Domain Protein

scholarly journals Differential physiological roles for BIN1 isoforms in skeletal muscle development, function and regeneration

2020 ◽  
Vol 13 (11) ◽  
pp. dmm044354
Author(s):  
Ivana Prokic ◽  
Belinda S. Cowling ◽  
Candice Kutchukian ◽  
Christine Kretz ◽  
Hichem Tasfaout ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Development ◽  
Membrane Remodeling ◽  
Skeletal Muscle Development ◽  
Developmental Defects ◽  
Intracellular Organization ◽  
T Tubules ◽  
And Function ◽  
Fine Tune

ABSTRACTSkeletal muscle development and regeneration are tightly regulated processes. How the intracellular organization of muscle fibers is achieved during these steps is unclear. Here, we focus on the cellular and physiological roles of amphiphysin 2 (BIN1), a membrane remodeling protein mutated in both congenital and adult centronuclear myopathies (CNM), that is ubiquitously expressed and has skeletal muscle-specific isoforms. We created and characterized constitutive muscle-specific and inducible Bin1 homozygous and heterozygous knockout mice targeting either ubiquitous or muscle-specific isoforms. Constitutive Bin1-deficient mice died at birth from lack of feeding due to a skeletal muscle defect. T-tubules and other organelles were misplaced and altered, supporting a general early role for BIN1 in intracellular organization, in addition to membrane remodeling. Although restricted deletion of Bin1 in unchallenged adult muscles had no impact, the forced switch from the muscle-specific isoforms to the ubiquitous isoforms through deletion of the in-frame muscle-specific exon delayed muscle regeneration. Thus, ubiquitous BIN1 function is necessary for muscle development and function, whereas its muscle-specific isoforms fine tune muscle regeneration in adulthood, supporting that BIN1 CNM with congenital onset are due to developmental defects, whereas later onset may be due to regeneration defects.

scholarly journals Caveolin-3 KO disrupts t-tubule structure and decreases t-tubular ICa density in mouse ventricular myocytes

2018 ◽  
Vol 315 (5) ◽  
pp. H1101-H1111 ◽  
Author(s):  
Simon M. Bryant ◽  
Cherrie H. T. Kong ◽  
Judy J. Watson ◽  
Hanne C. Gadeberg ◽  
David M. Roth ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Ventricular Myocytes ◽  
Wild Type ◽  
Tubule Formation ◽  
Membrane Area ◽  
Cellular Hypertrophy ◽  
Channel Expression ◽  
T Tubules ◽  
And Function

Caveolin-3 (Cav-3) is a protein that has been implicated in t-tubule formation and function in cardiac ventricular myocytes. In cardiac hypertrophy and failure, Cav-3 expression decreases, t-tubule structure is disrupted, and excitation-contraction coupling is impaired. However, the extent to which the decrease in Cav-3 expression underlies these changes is unclear. We therefore investigated the structure and function of myocytes isolated from the hearts of Cav-3 knockout (KO) mice. These mice showed cardiac dilatation and decreased ejection fraction in vivo compared with wild-type control mice. Isolated KO myocytes showed cellular hypertrophy, altered t-tubule structure, and decreased L-type Ca2+ channel current ( ICa) density. This decrease in density occurred predominantly in the t-tubules, with no change in total ICa, and was therefore a consequence of the increase in membrane area. Cav-3 KO had no effect on L-type Ca2+ channel expression, and C3SD peptide, which mimics the scaffolding domain of Cav-3, had no effect on ICa in KO myocytes. However, inhibition of PKA using H-89 decreased ICa at the surface and t-tubule membranes in both KO and wild-type myocytes. Cav-3 KO had no significant effect on Na+/Ca2+ exchanger current or Ca2+ release. These data suggest that Cav-3 KO causes cellular hypertrophy, thereby decreasing t-tubular ICa density. NEW & NOTEWORTHY Caveolin-3 (Cav-3) is a protein that inhibits hypertrophic pathways, has been implicated in the formation and function of cardiac t-tubules, and shows decreased expression in heart failure. This study demonstrates that Cav-3 knockout mice show cardiac dysfunction in vivo, while isolated ventricular myocytes show cellular hypertrophy, changes in t-tubule structure, and decreased t-tubular L-type Ca2+ current density, suggesting that decreased Cav-3 expression contributes to these changes in cardiac hypertrophy and failure.

scholarly journals An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1

Cell Reports ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 2056-2069 ◽  
Author(s):  
Rasmus Herlo ◽  
Viktor K. Lund ◽  
Matthew D. Lycas ◽  
Anna M. Jansen ◽  
George Khelashvili ◽  
...  
Keyword(s):  
Cellular Membrane ◽  
Membrane Curvature ◽  
Amphipathic Helix ◽  
Bar Domain ◽  
Curvature Sensing ◽  
Domain Protein ◽  
And Function

scholarly journals Essential Role of Septin 7 in Skeletal Muscle Structure and Function

2020 ◽  
Vol 118 (3) ◽  
pp. 258a
Author(s):  
Laszlo Csernoch ◽  
Mónika Gönczi ◽  
Zsolt Ráduly ◽  
László Szabó ◽  
Nóra Dobrosi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Essential Role ◽  
Structure And Function ◽  
Muscle Structure ◽  
And Function

scholarly journals Mapping of the contraction-induced phosphoproteome identifies TRIM28 as a significant regulator of skeletal muscle size and function

Cell Reports ◽  
2021 ◽  
Vol 34 (9) ◽  
pp. 108796
Author(s):  
Nathaniel D. Steinert ◽  
Gregory K. Potts ◽  
Gary M. Wilson ◽  
Amelia M. Klamen ◽  
Kuan-Hung Lin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Size ◽  
And Function

scholarly journals Alterations in intestinal microbiota diversity, composition, and function in patients with sarcopenia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lin Kang ◽  
Pengtao Li ◽  
Danyang Wang ◽  
Taihao Wang ◽  
Dong Hao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
16S Rrna ◽  
Intestinal Microbiota ◽  
Muscle Growth ◽  
Growth Function ◽  
16S Rrna Sequencing ◽  
Fecal Samples ◽  
Lipopolysaccharide Biosynthesis ◽  
Rrna Sequencing ◽  
And Function

Abstract16S rRNA sequencing of human fecal samples has been tremendously successful in identifying microbiome changes associated with both aging and disease. A number of studies have described microbial alterations corresponding to physical frailty and nursing home residence among aging individuals. A gut-muscle axis through which the microbiome influences skeletal muscle growth/function has been hypothesized. However, the microbiome has yet to be examined in sarcopenia. Here, we collected fecal samples of 60 healthy controls (CON) and 27 sarcopenic (Case)/possibly sarcopenic (preCase) individuals and analyzed the intestinal microbiota using 16S rRNA sequencing. We observed an overall reduction in microbial diversity in Case and preCase samples. The genera Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, and Lachnoclostridium—known butyrate producers—were significantly less abundant in Case and preCase subjects while Lactobacillus was more abundant. Functional pathways underrepresented in Case subjects included numerous transporters and phenylalanine, tyrosine, and tryptophan biosynthesis suggesting that protein processing and nutrient transport may be impaired. In contrast, lipopolysaccharide biosynthesis was overrepresented in Case and PreCase subjects suggesting that sarcopenia is associated with a pro-inflammatory metagenome. These analyses demonstrate structural and functional alterations in the intestinal microbiota that may contribute to loss of skeletal muscle mass and function in sarcopenia.

PROLONGED INTRAVENOUS INFUSION OF LABELLED IODOCOMPOUNDS IN THE RAT: [125I]IODIDE METABOLISM AND EFFECTS OF MODERATE DIETARY IODINE DEFICIENCY

1979 ◽  
Vol 82 (2) ◽  
pp. 227-234 ◽  
Author(s):  
VIPA BOONNAMSIRI ◽  
J. C. KERMODE ◽  
B. D. THOMPSON
Keyword(s):  
Skeletal Muscle ◽  
Iodine Deficiency ◽  
Intravenous Infusion ◽  
Structure And Function ◽  
Continuous Intravenous Infusion ◽  
Close Approximation ◽  
Faecal Excretion ◽  
And Function ◽  
Layer Chromatography ◽  
Secretion Rates

SUMMARY Radio-iodide was administered by prolonged continuous intravenous infusion to rats maintained under iodine-replete conditions and in moderate iodine deficiency. A close approximation to equilibrium labelling was thereby achieved. Labelled iodocompounds extracted from various tissues were analysed by thin-layer chromatography. Moderate iodine deficiency resulted in a slight increase in the ratio of mono-iodotyrosine to di-iodotyrosine in the thyroid. No change in the ratio of tri-iodothyronine (T3) to thyroxine (T4) was found in thyroid, plasma or skeletal muscle. Faecal excretion of T3 declined appreciably relative to that of T4. Under iodine-replete conditions the ratio of thyroidal secretion rates of T3 and T4 was estimated to be more than three times higher than the ratio of these iodocompounds within the thyroid. Heterogeneity of thyroglobulin structure and function may explain these observations.

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