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.
Citation
Stevenson, N.L., Bergen, D.J.M., Lu, Y., Prada-Sanchez, M.E., Kadler, K.E., Hammond, C.L., Stephens, D.J. (2021) Giantin is required for intracellular N-terminal processing of type I procollagen. The Journal of cell biology. 220(6).
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping