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UNC-45: A Chaperone for Myosin and a Co-Chaperone for Hsp90

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Networking of Chaperones by Co-Chaperones

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

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Abstract

UNC-45 is a prototype of the protein family characterized by the presence of the C-terminal UCS (UNC-45/CR01/She4p) domain. These proteins function in various important actin- and myosin-dependent cellular processes that include myofibril organization and muscle functions, cell differentiation, embryonic development, cytokinesis and endocytosis. Mutations in the genes that code for UCS domain proteins cause serious defects in these actomyosin-based processes. Homologs of UCS domain proteins have been identified in fungi, nematodes, insects, fish, amphibians, birds and mammals. In addition to the UCS domain, the animal homologs (UNC-45) contain an N-terminal TPR domain and a conserved central region. UNC-45 has been shown to act as chaperone to fold the heads of myosin heavy chain of various types. Apart from assisting myosin heads to fold correcdy, UNC-45 is known to bind Hsp90 direcdy and several UCS protein complexes appear to be dependent on the Hsp90 chaperone machinery. These findings suggest that UNC-45 and other proteins containing the UCS domain are a new class of Hsp90 co-chaperones.

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References

  1. Hutagalung AH, Landsverk ML, Price MG et al. The UCS family of myosin chaperones. J Cell Sci 2002; 115:3983–3990.

    Article  CAS  PubMed  Google Scholar 

  2. Yu QI, Bernstein SI. UCS proteins: Managing the myosin. Curr Biol 2003; 13:525–527.

    Article  Google Scholar 

  3. Das AK, Cohen PTW, Barford D. The structure of the tetratricopeptide repeats of protein phosphatase 5, implications for TPR-mediated protein-protein interactions. EMBO J 1998; 17:1192–1199.

    Article  CAS  PubMed  Google Scholar 

  4. Price MG, Landsverk ML, Barral JM et al. Two mammalian UNC-45 isoforms are related to distinct cytoskeletal and muscle-specific functions. J Cell Sci 2002; 115:4013–4023.

    Article  CAS  PubMed  Google Scholar 

  5. Balasubramanian MK, McCollum D, Chang L et al. Isolation and characterization of new fission yeast cytokinesis mutants. Genetics 1998; 149:1265–1275.

    CAS  PubMed  Google Scholar 

  6. Jansen RP, Dowzer C, Michaelis C et al. Mother cell-specific HO expression in budding yeast depends on the unconventional myosin myo4p and other cytoplasmic proteins. Cell 1996; 84:651–654.

    Article  Google Scholar 

  7. Wendland B, McCaffery JM, Xiao Q et al. A novel fluorescence-activated cell sorter-based screen for yeast endocytosis mutants identifies a yeast homologue of mammalian eps15. J Cell Biol 1996; 135:1485–1500.

    Article  CAS  PubMed  Google Scholar 

  8. Berteaux-Lecellier V, Zickler D, Debuchy R et al. A homologue of the yeast SHE4 gene is essential for the transition between the syncytial and cellular stages during sexual reproduction of the fungus Podospora anserina. EMBO J 1998; 17:1248–1258.

    Article  CAS  PubMed  Google Scholar 

  9. Epstein HF, Thomson JN. Temperature-sensitive mutation affecting myofilament assembly in Caenorhabditis elegans. Nature 1974; 250:579–580.

    Article  CAS  PubMed  Google Scholar 

  10. Kachur T, Ao W, Berger J et al. Maternal UNC-45 is involved in cytokinesis and colocalizes with nonmuscle myosin in the early Caenorhabditis elegans embryo. J Cell Sci 2004; 117:5313–5321.

    Article  CAS  PubMed  Google Scholar 

  11. Barral JM, Hutagalumg AH, Brinker A et al. Role of myosin assembly protein UNC-45 as a molecular chaperone for myosin. Science 2002; 295:669–671.

    Article  CAS  PubMed  Google Scholar 

  12. Mishra M, D’souza VM, Chang KC et al. Hsp90 protein in fission yeast Swolp and UCS protein Rng3p facilitate myosin II assembly and function. Eukaryot Cell 2005; 4:567–576.

    Article  CAS  PubMed  Google Scholar 

  13. Wesche S, Arnold M, Jansen RP. The UCS domain protein She4p binds to myosin motor domains and is essential for class I and class V myosin function. Curr Biol 2003; 13:715–724.

    Article  CAS  PubMed  Google Scholar 

  14. Yu Q, Hipolito LC, Kronert WA et al. Characterization and functional analysis of the Drosophila melanogaster unc-45 (dunc-45) gene. Mol Biol Cell 2003; 14:45.

    Article  Google Scholar 

  15. Landsverk ML, Epstein HF. Genetic analysis of myosin II assembly and organization in model organisms. Cell Mol Life Sci 2005; 62:2270–2282.

    Article  CAS  PubMed  Google Scholar 

  16. Kuczmarski ER, Spudich JA. Regulation of myosin self-assembly: Phosphorylation of Dictyostelium heavy chain inhibits formation of thick filaments. Proc Natl Acad Sci USA 1980; 77:7292–7296.

    Article  CAS  PubMed  Google Scholar 

  17. Srikakulam R, Winkelmann DA. Myosin II folding is mediated by a molecular chaperonin. J Biol Chem 1999; 274:27265–27273.

    Article  CAS  PubMed  Google Scholar 

  18. Rayment I, Rypniewski WR, Schmidt-Base K et al. Three-dimensional structure of myosin subfragment-1: A molecular motor. Science 1993; 261:50–58.

    Article  CAS  PubMed  Google Scholar 

  19. Rayment I, Holden HM, Whittaker M et al. Structure of the actin-myosin complex and its implications for muscle contraction. Science 1993; 261:58–65.

    Article  CAS  PubMed  Google Scholar 

  20. Atkinson SJ, Stewart M. Expression in Escherichia coli of fragments of the coiled-coil rod domain of rabbit myosin: Influence of different regions of the molecule on aggregation and paracrystal formation. J Cell Sci 1991; 99:823–836.

    CAS  PubMed  Google Scholar 

  21. Saraswat LD, Lowey S. Engineered cysteine mutants of myosin light chain 2: Fluorescent analogue for structural studies. J Biol Chem 1991; 266:19777–19785.

    CAS  PubMed  Google Scholar 

  22. McNally EM, Goodwin EB, Spudich JA et al. Coexpression and assembly of myosin heavy chain and myosin light chain in Escherichia coli. Proc Natl Acad Sci 1988; 85:7270–7273.

    Article  CAS  PubMed  Google Scholar 

  23. Mitchell EJ, Karn J, Brown DM et al. Regulatory and essential light-chain-binding sites in myosin heavy chain subfragment-1 mapped by site-directed mutagenesis. J Mol Biol 1989; 208:199–205.

    Article  CAS  PubMed  Google Scholar 

  24. Trybus KM. Regulation of expressed truncated smooth muscle myosins. Role of the essential light chain and tail length. J Biol Chem 1994; 269:20819–20822.

    CAS  PubMed  Google Scholar 

  25. Sweeney HL, Rosenfeld SS, Brown F et al. Kinetic tuning of myosin via a flexible loop adjacent to the nucleotide binding pocket. J Biol Chem 1998; 273:6262–6270.

    Article  CAS  PubMed  Google Scholar 

  26. Wang F, Chen L, Arcucci O et al. Effect of ADP and ionic strength on the kinetic and motile properties of recombinant mouse myosin V. J Biol Chem 2000; 275:4329–4335.

    Article  CAS  PubMed  Google Scholar 

  27. Kinose F, Wang SX, Kidambi US. Glycine 699 is pivotal for the motor activity of skeletal muscle myosin. J Cell Biol 1996; 134:895–909.

    Article  CAS  PubMed  Google Scholar 

  28. Chow D, Srikakulam R, Chen Y et al. Folding of the striated muscle myosin motor domain. J Biol Chem 2002; 277:36799–36807.

    Article  CAS  PubMed  Google Scholar 

  29. Srikakulam R, Winkelmann DA. Chaperone-mediated folding and assembly of myosin in striated muscle. J Cell Sci 2004; 117:641–652.

    Article  CAS  PubMed  Google Scholar 

  30. Chen S, Smith DF. Hop as an adaptor in the heat shock protein 70 (hsp70) and hsp90 chaperone machinery. J Biol Chem 1998; 273:35194–35200.

    Article  CAS  PubMed  Google Scholar 

  31. Morishima Y, Murphy PJ, Li DP et al. Stepwise assembly of a glucocorticoid receptor.hsp90 heterocomplex resolves two sequential ATP-dependent events involving first hsp70 and then hsp90 in opening of the steroid binding pocket. J Biol Chem 2000; 275:18054–18060.

    Article  CAS  PubMed  Google Scholar 

  32. Young JC, Moarefi I, Hartl FU. Hsp90: A specialized but essential protein-folding tool. J Cell Biol 2001; 154:267–273.

    Article  CAS  PubMed  Google Scholar 

  33. Blatch GL, Lassie M. The tetratricopeptide repeat: A structural motif mediating protein-protein interactions. BioEssays 1999; 21:932–939.

    Article  CAS  PubMed  Google Scholar 

  34. Smith DF. Tetratricopeptide repeat co-chaperones in steroid receptor complexes. Cell Stress Chap 2004; 9:109–121.

    Article  CAS  Google Scholar 

  35. Hoppe T, Cassata G, Barral JM et al. Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans. Cell 2004; 118:337–349.

    Article  CAS  PubMed  Google Scholar 

  36. Lord M, Pollard TD. UCS protein Rng3p activates actin filament gliding by fission yeast myosin-II. J Cell Biol 2004; 167:315–321.

    Article  CAS  PubMed  Google Scholar 

  37. Millson SH, Truman AW, King V et al. A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpklp). Eukaryot Cell 2005; 4:849–860.

    Article  CAS  PubMed  Google Scholar 

  38. Bose S, Weikl T, Bugl H et al. Chaperone function of Hsp90-associated proteins. Science 1996; 274:1715–1717.

    Article  CAS  PubMed  Google Scholar 

  39. Freeman BC, Toft DO, Morimoto RI. Molecular chaperone machines: Chaperone activities of the cyclophilin Cyp-40 and the steroid aporeceptor-associated protein p23. Science 1996; 274:1718–1720.

    Article  CAS  PubMed  Google Scholar 

  40. Kimura Y, Rutherford SL, Miyata Y. Cdc37 is a molecular chaperone with specific functions in signal transductions. Genes Dev 1997; 11:1775–1785.

    Article  CAS  PubMed  Google Scholar 

  41. Venolia L, Waterston RH. The unc-45 gene of Caenorhabditis elegans is an essential muscle-affecting gene with maternal expression. Genetics 1990; 126:345–353.

    CAS  PubMed  Google Scholar 

  42. Barral JM, Bauer CC, Ortiz I et al. Unc-45 mutations in Caenorhabditis elegans implicate a CROl/ She4p-like domain in myosin assembly. J Cell Biol 1998; 143:1215–1225.

    Article  CAS  PubMed  Google Scholar 

  43. Waterston RH. Muscle. In: Wood WB, ed. The Nematode Caenorhabditis elegans. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory, 1988:281–335.

    Google Scholar 

  44. Waterston RH, Thomson JN, Brenner S. Mutants with altered muscle structure in Caenorhabditis elegans. Dev Biol 1980; 77:271–302.

    Article  CAS  PubMed  Google Scholar 

  45. Schachat F, Harris HE, Epstein HF. Two homogeneous myosins in body-wall muscle of Caenorhabditis elegans. Cell 1977; 10:721–728.

    Article  CAS  PubMed  Google Scholar 

  46. Miller DM, Ortiz L, Berliner GC et al. Differential localization of two myosins within nematode thick filaments. Cell 1983; 34:477–490.

    Article  CAS  PubMed  Google Scholar 

  47. Waterston RH. The minor myosin heavy chain, mhcA, of Caenorhabditis elegans is necessary for the initiation of thick filament assembly. EMBO J 1989; 8:3429–3436.

    CAS  PubMed  Google Scholar 

  48. Ardizzi JP, Epstein HF. Immunochemical localization of myosin heavy chain isoforms and paramyosin in developmentally and structurally diverse muscle cell types of the nematode Caenorhabditis elegans. J Cell Biol 1987; 105:2763–2770.

    Article  CAS  PubMed  Google Scholar 

  49. Venolia L, Ao W, Kim S et al. unc-45 gene of Caenorhabditis elegans encodes a muscle-specific tetratricopeptide repeat-containing protein. Cell Mot Cytoskeleton 1999; 42:163–177.

    Article  CAS  Google Scholar 

  50. Ao W, Pilgrim D. Caenorhabditis elegans UNC-45 is a component of muscle thick filaments and colocalizes with myosin heavy chain B, but not myosin heavy chain A. J Cell Biol 2000; 148:375–384.

    Article  CAS  PubMed  Google Scholar 

  51. Guo S, Kemphues KJ. A nonmuscle myosin required for embryonic polarity in Caenorhabditis elegans. Nature 1996; 382:455–458.

    Article  CAS  PubMed  Google Scholar 

  52. Sikorski RS, Boguski MS, Goebl M. A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 1990; 60:307–317.

    Article  CAS  PubMed  Google Scholar 

  53. Scheufler C, Brinker A, Bourenkov G et al. Structure of TPR domain-peptide complexes: Critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 2000; 101:199–210.

    Article  CAS  PubMed  Google Scholar 

  54. Wong KCY, Naqvi NI, Lino Y et al. Fission yeast Rng3p: An UCS-domain protein that mediates myosin II assembly during cytokinesis. J Cell Sci 2000; 113:2421–2432.

    CAS  PubMed  Google Scholar 

  55. Young JC, Barral JM, Hard FU. More than folding: Localized functions of cytosolic chaperones. TIBS 2003; 28:541–547.

    CAS  PubMed  Google Scholar 

  56. Toi H, Fujimura-Kamada K, Irie K et al. She4p/Dimlp interacts with the motor domain of unconventional myosins in the budding yeast, Saccharomyces cerevisiae. Mol Biol Cell 2003; 14:2237–2249.

    Article  CAS  PubMed  Google Scholar 

  57. Wong KCY, D’souza VM, Naqvi NI et al. Importance of a myosin Il-containing progenitor for actomyosin ring assembly in fission yeast. Curr Biol 2002; 12:724–729.

    Article  CAS  PubMed  Google Scholar 

  58. Pratt WB, Toft DO. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 1997; 18:306–360.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neuroscience and Cell Biology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, Texas, 77555-0625, USA

    Odutayo O. Odunuga & Henry F. Epstein

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  1. Odutayo O. Odunuga
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  2. Henry F. Epstein
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© 2007 Landes Bioscience and Springer Science+Business Media

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Odunuga, O.O., Epstein, H.F. (2007). UNC-45: A Chaperone for Myosin and a Co-Chaperone for Hsp90. In: Networking of Chaperones by Co-Chaperones. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-49310-7_6

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