title: Dysferlin Binds SNAREs (Soluble N-Ethylmaleimide-sensitive Factor (NSF) Attachment Protein Receptors) and Stimulates Membrane Fusion in a Calcium-sensitive Manner.
abstract: Resealing of tears in the sarcolemma of myofibers is a necessary step in the repair of muscle tissue. Recent work suggests a critical role for dysferlin in the membrane repair process and that mutations in dysferlin are responsible for limb girdle muscular dystrophy 2B and Miyoshi myopathy. Beyond membrane repair, dysferlin has been linked to SNARE-mediated exocytotic events including cytokine release and acid sphingomyelinase secretion. However, it is unclear whether dysferlin regulates SNARE-mediated membrane fusion. In this study we demonstrate a direct interaction between dysferlin and the SNARE proteins syntaxin 4 and SNAP-23. In addition, analysis of FRET and in vitro reconstituted lipid mixing assays indicate that dysferlin accelerates syntaxin 4/SNAP-23 heterodimer formation and SNARE-mediated lipid mixing in a calcium-sensitive manner. These results support a function for dysferlin as a calcium-sensing SNARE effector for membrane fusion events.
authors.affiliation: From the Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Codding
authors.affiliation: From the Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331.
authors.forename: Naomi
authors.initials: N
authors.lastname: Marty
authors.affiliation: From the Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331.
authors.forename: Nazish
authors.initials: N
authors.lastname: Abdullah
authors.affiliation: From the Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331 colin.johnson@oregonstate.edu.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Johnson
mesh_terms: D002118:Calcium / Q000378:metabolism*; D019281:Dimerization; D000073939:Dysferlin; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D050356:Lipid Metabolism; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism*
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D050600:SNARE Proteins; D052066:N-Ethylmaleimide-Sensitive Proteins; D002118:Calcium
keywords: SNARE proteins; calcium-binding protein; dysferlin; exocytosis; membrane fusion; muscular dystrophy