title: Dysferlin function in skeletal muscle: Possible pathological mechanisms and therapeutical targets in dysferlinopathies.
abstract: Mutations in the dysferlin gene are linked to a group of muscular dystrophies known as dysferlinopathies. These myopathies are characterized by progressive atrophy. Studies in muscle tissue from dysferlinopathy patients or dysferlin-deficient mice point out its importance in membrane repair. However, expression of dysferlin homologous proteins that restore sarcolemma repair function in dysferlinopathy animal models fail to arrest muscle wasting, therefore suggesting that dysferlin plays other critical roles in muscle function. In the present review, we discuss dysferlin functions in the skeletal muscle, as well as pathological mechanisms related to dysferlin mutations. Particular focus is presented related the effect of dysferlin on cell membrane related function, which affect its repair, vesicle trafficking, as well as Ca(2+) homeostasis. Such mechanisms could provide accessible targets for pharmacological therapies.
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile. Electronic address: ana.cardenas@uv.cl.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cárdenas
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile; Programa de Anatomía y Biología del Desarrollo, ICBM, Facultad de Medicina, Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile.
authors.forename: Arlek M
authors.initials: AM
authors.lastname: González-Jamett
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, ICBM, Facultad de Medicina, Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Cea
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, ICBM, Facultad de Medicina, Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Bevilacqua
authors.affiliation: Programa de Farmacología Molecular y Clinica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Caviedes
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D000073939:Dysferlin; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000235:genetics*
chemical_list: D017630:Connexins; C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D002118:Calcium
keywords: Connexin hemichannels; Dysferlin; Dysferlinopathies; Inflammatory processes; Membrane repair; Muscular dystrophies; Vesicle trafficking