title: Hsp47 and other ER-resident molecular chaperones form heterocomplexes with each other and with collagen type IV chains.
abstract: Collagen type IV is a genetically distinct secretory protein that constitutes a major component of the basement membranes. Despite the differences between collagen types I and IV, it appears that collagen IV alpha-chain translation/translocation through the ER should follow similar pathways to those established for procollagen I. Using a collagen IV-producing mouse teratocarcinoma cell line, we sought to determine if evolving nascent chains of collagen IV are associated with Hsp47 and other ER-resident molecular chaperones. We show that Hsp47, Grp78 and Grp94 appear to form heteromeric complexes associated with each other and with nascent chains of collagen IV. In addition, we investigated whether ATP depletion, a condition known to promote stable association of Grp78 and Grp94 proteins with their chaperone substrates, extended this response to include a chaperone independent of ATP, Hsp47. These studies reveal that ATP depletion increased the levels of newly synthesized collagen IV associated with Hsp47, Grp78, Grp94 and with each other. These results indicate that Hsp47, Grp78 and Grp94 exist as oligomers and form heterocomplexes during the maturation of newly synthesized collagen IV chains.
authors.affiliation: Department of Oral Pathology, University of Maryland at Baltimore 21201, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Ferreira
authors.forename: K
authors.initials: K
authors.lastname: Norris
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: C
authors.initials: C
authors.lastname: Hebert
authors.forename: J J
authors.initials: JJ
authors.lastname: Sauk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D011132:Polyribosomes; D012343:RNA, Transfer / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; C494661:Serpinh1 protein, mouse; C494662:Serpinh1 protein, rat; D000255:Adenosine Triphosphate; D003094:Collagen; D012343:RNA, Transfer