title: The balanced regulation of Hsc70 by DNJ-13 and UNC-23 is required for muscle functionality.
abstract: The molecular chaperone Hsc70 assists in the folding of non-native proteins together with its J domain- and BAG domain-containing cofactors. In Caenorhabditis elegans, two BAG domain-containing proteins can be identified, one of them being UNC-23, whose mutation induces severe motility dysfunctions. Using reporter strains, we find that the full-length UNC-23, in contrast to C-terminal fragments, localizes specifically to the muscular attachment sites. C-terminal fragments of UNC-23 instead perform all Hsc70-related functions, like ATPase stimulation and regulation of folding activity, albeit with lower affinity than BAG-1. Interestingly, overexpression of CFP-Hsc70 can induce muscular defects in wild-type nematodes that phenocopy the knockout of its cofactor UNC-23. Strikingly, the motility dysfunction in the unc-23 mutated strain can be cured specifically by down-regulation of the antagonistic Hsc70 cochaperone DNJ-13, implying that the severe phenotype is caused by misregulation of the Hsc70 cycle. These findings point out that the balanced action of cofactors in the ATP-driven cycle of Hsc70 is crucial for the contribution of Hsc70 to muscle functionality.
authors: From the Department of Biotechnology and Center for Integrated Protein Science Munich (CIPS), Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors: Katharina
authors: K
authors: Papsdorf
authors: From the Department of Biotechnology and Center for Integrated Protein Science Munich (CIPS), Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors: Julia
authors: J
authors: Sacherl
authors: From the Department of Biotechnology and Center for Integrated Protein Science Munich (CIPS), Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany klaus.richter@richterlab.de.
authors: Klaus
authors: K
authors: Richter
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009132:Muscles / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D013550:Swimming / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D008164:Luminescent Proteins; C083141:phorbol ester binding protein; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases
keywords: Bag2; Caenorhabditis elegans (C. elegans); Heat Shock Protein (HSP); Molecular Chaperone; Muscular Dystrophy; Shear Stress