title: Clathrin isoform CHC22, a component of neuromuscular and myotendinous junctions, binds sorting nexin 5 and has increased expression during myogenesis and muscle regeneration.
abstract: 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.
authors.affiliation: The G.W. Hooper Foundation, Department of Microbiology and Immunology and Department of Biopharmaceutical Sciences, University of California, San Francisco, California 94143-0552, USA.
authors.forename: Mhairi C
authors.initials: MC
authors.lastname: Towler
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gleeson
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hoshino
authors.forename: Paavo
authors.initials: P
authors.lastname: Rahkila
authors.forename: Venus
authors.initials: V
authors.lastname: Manalo
authors.forename: Norio
authors.initials: N
authors.lastname: Ohkoshi
authors.forename: Charles
authors.initials: C
authors.lastname: Ordahl
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Frances M
authors.initials: FM
authors.lastname: Brodsky
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism*; D033922:Clathrin Heavy Chains / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004179:Cobra Cardiotoxin Proteins / Q000494:pharmacology; D003893:Desmin / Q000032:analysis / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000032:analysis / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000378:metabolism; D024510:Muscle Development; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D064231:Nestin; D009469:Neuromuscular Junction / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D012038:Regeneration; D058305:Sorting Nexins; D013710:Tendons / Q000276:immunology / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins
chemical_list: C101272:CLTCL1 protein, human; D002352:Carrier Proteins; D002966:Clathrin; D004179:Cobra Cardiotoxin Proteins; D003893:Desmin; D016023:Integrins; D007381:Intermediate Filament Proteins; D009124:Muscle Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; C402667:SNX5 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D033922:Clathrin Heavy Chains; C082908:integrin alpha7beta1