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New specific HSP47 functions in collagen subfamily chaperoning

Köhler, Anna ; Mörgelin, Matthias LU ; Gebauer, Jan M. ; Öcal, Sinan ; Imhof, Thomas ; Koch, Manuel ; Nagata, Kazuhiro ; Paulsson, Mats ; Zaucke, Frank and Baumann, Ulrich , et al. (2020) In FASEB Journal 34(9). p.12040-12052
Abstract

Although collagens are the most abundant proteins implicated in various disease pathways, essential mechanisms required for their proper folding and assembly are poorly understood. Heat-shock protein 47 (HSP47), an ER-resident chaperone, was mainly reported to fulfill key functions in folding and secretion of fibrillar collagens by stabilizing pro-collagen triple-helices. In this study, we demonstrate unique functions of HSP47 for different collagen subfamilies. Our results show that HSP47 binds to the N-terminal region of procollagen I and is essential for its secretion. However, HSP47 ablation does not majorly impact collagen VI secretion, but its lateral assembly. Moreover, specific ablation of Hsp47 in murine keratinocytes revealed... (More)

Although collagens are the most abundant proteins implicated in various disease pathways, essential mechanisms required for their proper folding and assembly are poorly understood. Heat-shock protein 47 (HSP47), an ER-resident chaperone, was mainly reported to fulfill key functions in folding and secretion of fibrillar collagens by stabilizing pro-collagen triple-helices. In this study, we demonstrate unique functions of HSP47 for different collagen subfamilies. Our results show that HSP47 binds to the N-terminal region of procollagen I and is essential for its secretion. However, HSP47 ablation does not majorly impact collagen VI secretion, but its lateral assembly. Moreover, specific ablation of Hsp47 in murine keratinocytes revealed a new role for the transmembrane collagen XVII triple-helix formation. Incompletely folded collagen XVII C-termini protruding from isolated HSP47 null keratinocyte membrane vesicles could be fully restored upon the application of recombinant HSP47. Thus, our study expands the current view regarding the client repertoire and function of HSP47, as well as emphasizes its importance for transmembrane collagen folding.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
collagen, collagen XVII, FACIT, HSP47, MACIT
in
FASEB Journal
volume
34
issue
9
pages
13 pages
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • scopus:85088574378
  • pmid:32716577
ISSN
0892-6638
DOI
10.1096/fj.202000570R
language
English
LU publication?
yes
id
a1a052b3-a831-44a2-a904-864ef216ec3d
date added to LUP
2020-08-06 12:23:06
date last changed
2022-08-03 23:59:48
@article{a1a052b3-a831-44a2-a904-864ef216ec3d,
  abstract     = {{<p>Although collagens are the most abundant proteins implicated in various disease pathways, essential mechanisms required for their proper folding and assembly are poorly understood. Heat-shock protein 47 (HSP47), an ER-resident chaperone, was mainly reported to fulfill key functions in folding and secretion of fibrillar collagens by stabilizing pro-collagen triple-helices. In this study, we demonstrate unique functions of HSP47 for different collagen subfamilies. Our results show that HSP47 binds to the N-terminal region of procollagen I and is essential for its secretion. However, HSP47 ablation does not majorly impact collagen VI secretion, but its lateral assembly. Moreover, specific ablation of Hsp47 in murine keratinocytes revealed a new role for the transmembrane collagen XVII triple-helix formation. Incompletely folded collagen XVII C-termini protruding from isolated HSP47 null keratinocyte membrane vesicles could be fully restored upon the application of recombinant HSP47. Thus, our study expands the current view regarding the client repertoire and function of HSP47, as well as emphasizes its importance for transmembrane collagen folding.</p>}},
  author       = {{Köhler, Anna and Mörgelin, Matthias and Gebauer, Jan M. and Öcal, Sinan and Imhof, Thomas and Koch, Manuel and Nagata, Kazuhiro and Paulsson, Mats and Zaucke, Frank and Baumann, Ulrich and Sengle, Gerhard}},
  issn         = {{0892-6638}},
  keywords     = {{collagen; collagen XVII; FACIT; HSP47; MACIT}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{12040--12052}},
  publisher    = {{The Federation of American Societies for Experimental Biology}},
  series       = {{FASEB Journal}},
  title        = {{New specific HSP47 functions in collagen subfamily chaperoning}},
  url          = {{http://dx.doi.org/10.1096/fj.202000570R}},
  doi          = {{10.1096/fj.202000570R}},
  volume       = {{34}},
  year         = {{2020}},
}