PUBLICATION

Giantin is required for intracellular N-terminal processing of type I procollagen

Authors
Stevenson, N.L., Bergen, D.J.M., Lu, Y., Prada-Sanchez, M.E., Kadler, K.E., Hammond, C.L., Stephens, D.J.
ID
ZDB-PUB-210505-6
Date
2021
Source
The Journal of cell biology   220(6): (Journal)
Registered Authors
Bergen, Dylan, Hammond, Chrissy, Stephens, David, Stevenson, Nicola
Keywords
none
MeSH Terms
  • Animals
  • Bone and Bones/metabolism*
  • CRISPR-Cas Systems
  • Collagen Type I/metabolism*
  • Extracellular Matrix/metabolism*
  • Golgi Matrix Proteins/antagonists & inhibitors
  • Golgi Matrix Proteins/genetics
  • Golgi Matrix Proteins/metabolism*
  • Humans
  • Procollagen/metabolism*
  • Zebrafish
PubMed
33944912 Full text @ J. Cell Biol.
Abstract
Knockout of the golgin giantin leads to skeletal and craniofacial defects driven by poorly studied changes in glycosylation and extracellular matrix deposition. Here, we sought to determine how giantin impacts the production of healthy bone tissue by focusing on the main protein component of the osteoid, type I collagen. Giantin mutant zebrafish accumulate multiple spontaneous fractures in their caudal fin, suggesting their bones may be more brittle. Inducing new experimental fractures revealed defects in the mineralization of newly deposited collagen as well as diminished procollagen reporter expression in mutant fish. Analysis of a human giantin knockout cell line expressing a GFP-tagged procollagen showed that procollagen trafficking is independent of giantin. However, our data show that intracellular N-propeptide processing of pro-α1(I) is defective in the absence of giantin. These data demonstrate a conserved role for giantin in collagen biosynthesis and extracellular matrix assembly. Our work also provides evidence of a giantin-dependent pathway for intracellular procollagen processing.
Errata / Notes
This article is corrected by ZDB-PUB-220906-247 .

Correction: https://rupress.org/jcb/article/220/7/jcb.20200516606072021c/212268/Correction-Giantin-is-required-for-intracellular-N Corrects Article: https://rupress.org/jcb/article/220/6/e202005166/212045/Giantin-is-required-for-intracellular-N-terminal
Genes / Markers
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Human Disease / Model
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Mapping