Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans

Thorsten Hoppe, Giuseppe Cassata, José M. Barral, Wolfdieter Springer, Alex H. Hutagalung, Henry F. Epstein, Ralf Baumeister

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

The organization of the motor protein myosin into motile cellular structures requires precise temporal and spatial control. Caenorhabditis elegans UNC-45 facilitates this by functioning both as a chaperone and as a Hsp90 cochaperone for myosin during thick filament assembly. Consequently, mutations in C. elegans unc-45 result in paralyzed animals with severe myofibril disorganization in striated body wall muscles. Here, we report a new E3/E4 complex, formed by CHN-1, the C. elegans ortholog of CHIP (carboxyl terminus of Hsc70-interacting protein), and UFD-2, an enzyme known to have ubiquitin conjugating E4 activity in yeast, as necessary and sufficient to multiubiquitylate UNC-45 in vitro. The phenotype of unc-45 temperature-sensitive animals is partially suppressed by chn-1 loss of function, while UNC-45 overexpression in worms deficient for chn-1 results in severely disorganized muscle cells. These results identify CHN-1 and UFD-2 as a functional E3/E4 complex and UNC-45 as its physiologically relevant substrate.

Original languageEnglish (US)
Pages (from-to)337-349
Number of pages13
JournalCell
Volume118
Issue number3
DOIs
StatePublished - Aug 6 2004
Externally publishedYes

Fingerprint

Caenorhabditis elegans
Myosins
Muscle
Animals
HSC70 Heat-Shock Proteins
Ubiquitin
Yeast
Proteins
Myofibrils
Cells
Cellular Structures
Muscle Cells
Substrates
Enzymes
Yeasts
Phenotype
Muscles
Mutation
Temperature

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Hoppe, T., Cassata, G., Barral, J. M., Springer, W., Hutagalung, A. H., Epstein, H. F., & Baumeister, R. (2004). Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans. Cell, 118(3), 337-349. https://doi.org/10.1016/j.cell.2004.07.014

Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans. / Hoppe, Thorsten; Cassata, Giuseppe; Barral, José M.; Springer, Wolfdieter; Hutagalung, Alex H.; Epstein, Henry F.; Baumeister, Ralf.

In: Cell, Vol. 118, No. 3, 06.08.2004, p. 337-349.

Research output: Contribution to journalArticle

Hoppe, T, Cassata, G, Barral, JM, Springer, W, Hutagalung, AH, Epstein, HF & Baumeister, R 2004, 'Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans', Cell, vol. 118, no. 3, pp. 337-349. https://doi.org/10.1016/j.cell.2004.07.014
Hoppe T, Cassata G, Barral JM, Springer W, Hutagalung AH, Epstein HF et al. Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans. Cell. 2004 Aug 6;118(3):337-349. https://doi.org/10.1016/j.cell.2004.07.014
Hoppe, Thorsten ; Cassata, Giuseppe ; Barral, José M. ; Springer, Wolfdieter ; Hutagalung, Alex H. ; Epstein, Henry F. ; Baumeister, Ralf. / Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans. In: Cell. 2004 ; Vol. 118, No. 3. pp. 337-349.
@article{d23af373ce794e2d827ccab293522e05,
title = "Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans",
abstract = "The organization of the motor protein myosin into motile cellular structures requires precise temporal and spatial control. Caenorhabditis elegans UNC-45 facilitates this by functioning both as a chaperone and as a Hsp90 cochaperone for myosin during thick filament assembly. Consequently, mutations in C. elegans unc-45 result in paralyzed animals with severe myofibril disorganization in striated body wall muscles. Here, we report a new E3/E4 complex, formed by CHN-1, the C. elegans ortholog of CHIP (carboxyl terminus of Hsc70-interacting protein), and UFD-2, an enzyme known to have ubiquitin conjugating E4 activity in yeast, as necessary and sufficient to multiubiquitylate UNC-45 in vitro. The phenotype of unc-45 temperature-sensitive animals is partially suppressed by chn-1 loss of function, while UNC-45 overexpression in worms deficient for chn-1 results in severely disorganized muscle cells. These results identify CHN-1 and UFD-2 as a functional E3/E4 complex and UNC-45 as its physiologically relevant substrate.",
author = "Thorsten Hoppe and Giuseppe Cassata and Barral, {Jos{\'e} M.} and Wolfdieter Springer and Hutagalung, {Alex H.} and Epstein, {Henry F.} and Ralf Baumeister",
year = "2004",
month = "8",
day = "6",
doi = "10.1016/j.cell.2004.07.014",
language = "English (US)",
volume = "118",
pages = "337--349",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4-multiubiquitylation complex in C. elegans

AU - Hoppe, Thorsten

AU - Cassata, Giuseppe

AU - Barral, José M.

AU - Springer, Wolfdieter

AU - Hutagalung, Alex H.

AU - Epstein, Henry F.

AU - Baumeister, Ralf

PY - 2004/8/6

Y1 - 2004/8/6

N2 - The organization of the motor protein myosin into motile cellular structures requires precise temporal and spatial control. Caenorhabditis elegans UNC-45 facilitates this by functioning both as a chaperone and as a Hsp90 cochaperone for myosin during thick filament assembly. Consequently, mutations in C. elegans unc-45 result in paralyzed animals with severe myofibril disorganization in striated body wall muscles. Here, we report a new E3/E4 complex, formed by CHN-1, the C. elegans ortholog of CHIP (carboxyl terminus of Hsc70-interacting protein), and UFD-2, an enzyme known to have ubiquitin conjugating E4 activity in yeast, as necessary and sufficient to multiubiquitylate UNC-45 in vitro. The phenotype of unc-45 temperature-sensitive animals is partially suppressed by chn-1 loss of function, while UNC-45 overexpression in worms deficient for chn-1 results in severely disorganized muscle cells. These results identify CHN-1 and UFD-2 as a functional E3/E4 complex and UNC-45 as its physiologically relevant substrate.

AB - The organization of the motor protein myosin into motile cellular structures requires precise temporal and spatial control. Caenorhabditis elegans UNC-45 facilitates this by functioning both as a chaperone and as a Hsp90 cochaperone for myosin during thick filament assembly. Consequently, mutations in C. elegans unc-45 result in paralyzed animals with severe myofibril disorganization in striated body wall muscles. Here, we report a new E3/E4 complex, formed by CHN-1, the C. elegans ortholog of CHIP (carboxyl terminus of Hsc70-interacting protein), and UFD-2, an enzyme known to have ubiquitin conjugating E4 activity in yeast, as necessary and sufficient to multiubiquitylate UNC-45 in vitro. The phenotype of unc-45 temperature-sensitive animals is partially suppressed by chn-1 loss of function, while UNC-45 overexpression in worms deficient for chn-1 results in severely disorganized muscle cells. These results identify CHN-1 and UFD-2 as a functional E3/E4 complex and UNC-45 as its physiologically relevant substrate.

UR - http://www.scopus.com/inward/record.url?scp=4043096960&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4043096960&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2004.07.014

DO - 10.1016/j.cell.2004.07.014

M3 - Article

VL - 118

SP - 337

EP - 349

JO - Cell

JF - Cell

SN - 0092-8674

IS - 3

ER -