Consequences of a novel caveolin‐3 mutation in a large German family

Fischer, Dirk; Schroers, Anja; Blümcke, Ingmar; Urbach, Horst; Zerres, Klaus; Mortier, W.; Vorgerd, Matthias; Schröder, Rolf

doi:10.1002/ana.10442

Cited by 80 publications

(61 citation statements)

References 22 publications

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“…Cav-3 protein is 151 amino acids (aa) long and is divided in five separate domains: N-terminal (aa 1-53), scaffolding (aa [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73], transmembrane (aa 74-106), and C-terminal (aa 107-151). The N-terminal domain contains a signature sequence (aa 41-48, FED-VIAEP) that is present in all caveolins.…”

Section: Caveolin-3 In Muscle Development and Physiologymentioning

confidence: 99%

“…59 Notably, few CAV3 mutations are associated with LGMD-1C and different clinical phenotypes in the same family, and few patients display overlapping signs between LGMD and RMD. 43,60,61 HyperCKemia Isolated H-CK, that is, increased serum concentration of CK in the absence of any clinical findings of muscular disease can occur in simplex (that is, a single occurrence in a family) or familial cases.…”

Section: Caveolin-3 and Muscle Diseasesmentioning

confidence: 99%

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Caveolinopathies: from the biology of caveolin-3 to human diseases

et al. 2009

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Section: Caveolin-3 In Muscle Development and Physiologymentioning

confidence: 99%

Section: Caveolin-3 and Muscle Diseasesmentioning

confidence: 99%

Caveolinopathies: from the biology of caveolin-3 to human diseases

et al. 2009

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“…An emerging theme in muscle cell biology is that muscle-specific versions of ubiquitous membrane traffic components are responsible for aspects of the specialized membrane traffic involved in muscle function. Two examples include isoforms of amphiphysin and caveolin, which have been implicated in T-tubule development in nonhuman species (Parton et al, 1997;Zhang and Zelhof, 2002) and are defective in vertebrate muscle disease (Fischer et al, 2003;Kubisch et al, 2003;Muller et al, 2003). Here we characterize the distribution and function of the CHC22 isoform of clathrin heavy chain in skeletal muscle where it is preferentially expressed (Long et al, 1996;Sirotkin et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Clathrin Isoform CHC22, a Component of Neuromuscular and Myotendinous Junctions, Binds Sorting Nexin 5 and Has Increased Expression during Myogenesis and Muscle Regeneration

Towler

Gleeson

Hoshino

et al. 2004

MBoC

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The muscle isoform of clathrin heavy chain, CHC22, has 85% sequence identity to the ubiquitously expressed CHC17, yet its expression pattern and function appear to be distinct from those of well-characterized clathrin-coated vesicles. In mature muscle CHC22 is preferentially concentrated at neuromuscular and myotendinous junctions, suggesting a role at sarcolemmal contacts with extracellular matrix. During myoblast differentiation, CHC22 expression is increased, initially localized with desmin and nestin and then preferentially segregated to the poles of fused myoblasts. CHC22 expression is also increased in regenerating muscle fibers with the same time course as embryonic myosin, indicating a role in muscle repair. CHC22 binds to sorting nexin 5 through a coiled-coil domain present in both partners, which is absent in CHC17 and coincides with the region on CHC17 that binds the regulatory light-chain subunit. These differential binding data suggest a mechanism for the distinct functions of CHC22 relative to CHC17 in membrane traffic during muscle development, repair, and at neuromuscular and myotendinous junctions.

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“…Dysferlin and Cav3 have been co-purified from muscle cells (16,17) and shown to localize to adjacent membrane domains at the surface in mature muscle fibers (18). Moreover, dysferlin is depleted from the plasma membrane (PM) 2 when Cav3 is mutated (8,9,14,17,19). We have recently demonstrated a role for caveolin in dysferlin localization at the PM (18).…”

mentioning

confidence: 99%

Caveolin Regulates Endocytosis of the Muscle Repair Protein, Dysferlin

Hernández-Deviez

Howes

Laval

et al. 2008

Journal of Biological Chemistry

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Dysferlin and Caveolin-3 are plasma membrane proteins associated with muscular dystrophy. Patients with mutations in the CAV3 gene show dysferlin mislocalization in muscle cells. By utilizing caveolin-null cells, expression of caveolin mutants, and different mutants of dysferlin, we have dissected the site of action of caveolin with respect to dysferlin trafficking pathways. We now show that Caveolin-1 or -3 can facilitate exit of a dysferlin mutant that accumulates in the Golgi complex of Cav1 ؊/؊ cells. In contrast, wild type dysferlin reaches the plasma membrane but is rapidly endocytosed in Cav1 ؊/؊ cells. We demonstrate that the primary effect of caveolin is to cause surface retention of dysferlin. Caveolin-1 or Caveolin-3, but not specific caveolin mutants, inhibit endocytosis of dysferlin through a clathrin-independent pathway colocalizing with internalized glycosylphosphatidylinositol-anchored proteins. Our results provide new insights into the role of this endocytic pathway in surface remodeling of specific surface components. In addition, they highlight a novel mechanism of action of caveolins relevant to the pathogenic mechanisms underlying caveolin-associated disease.Dysferlin and Caveolin-3 (muscle-specific caveolin, Cav3) are sarcolemmal proteins whose role in muscle has gained clinical attention because mutations in their genes are associated with a number of muscle pathologies. Patients with mutations in the dysferlin (DYSF) gene develop disorders such as limb girdle muscular dystrophy type 2B, miyoshi myopathy, and distal myopathy (1-5). Whereas disruption in the Caveolin-3 (CAV3) gene has been linked to limb girdle muscular dystrophy 1C, Rippling muscle diseases, hyperCKemia, and distal myopathy among other myopathies (6 -15). Dysferlin and Cav3 have been co-purified from muscle cells (16,17) and shown to localize to adjacent membrane domains at the surface in mature muscle fibers (18). Moreover, dysferlin is depleted from the plasma membrane (PM) 2 when Cav3 is mutated (8,9,14,17,19). We have recently demonstrated a role for caveolin in dysferlin localization at the PM (18). However, the interplay of dysferlin and caveolin membrane trafficking dynamics remains to be examined.Dysferlin belongs to the ferlin family of proteins comprising otoferlin, myoferlin, and fer1L3 (20 -22). The DYSF gene encodes a 230-kDa skeletal muscle membrane protein (2, 5, 23) with homology to the Caenorhabditis elegans sperm-vesicle fusion factor, fer-1 (2). Because of this dysferlin has been suggested to play a role in vesicle fusion in skeletal muscle (2, 24). Moreover, in the absence of dysferlin muscle cells show defective resealing of membrane disruptions (25). Dysferlin has a single transmembrane domain at the C terminus and a long N-terminal cytoplasmic region containing six C2 domains. C2 domains are a common feature of the synaptotagmin family of proteins implicated in vesicular traffic and membrane fusion events through calcium-dependent interactions with phospholipids and proteins (26 -29). Interestingly, ...

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Consequences of a novel caveolin‐3 mutation in a large German family

Cited by 80 publications

References 22 publications

Caveolinopathies: from the biology of caveolin-3 to human diseases

Caveolinopathies: from the biology of caveolin-3 to human diseases

Clathrin Isoform CHC22, a Component of Neuromuscular and Myotendinous Junctions, Binds Sorting Nexin 5 and Has Increased Expression during Myogenesis and Muscle Regeneration

Caveolin Regulates Endocytosis of the Muscle Repair Protein, Dysferlin

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