PUBLICATION
Syntaxin 18 Defects in Human and Zebrafish Unravel Key Roles in Early Cartilage and Bone Development
- Authors
- Guillemyn, B., De Saffel, H., Bek, J.W., Tapaneeyaphan, P., De Clercq, A., Jarayseh, T., Debaenst, S., Willaert, A., De Rycke, R., Byers, P.H., Rosseel, T., Coucke, P., Blaumeiser, B., Syx, D., Malfait, F., Symoens, S.
- ID
- ZDB-PUB-231002-46
- Date
- 2023
- Source
- Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 38(11): 1718-1730 (Journal)
- Registered Authors
- Coucke, Paul, Willaert, Andy
- Keywords
- COLLAGEN, GENETIC ANIMAL MODELS, OSTEOGENESIS IMPERFECTA
- MeSH Terms
-
- Animals
- Bone Development
- Cartilage/metabolism
- Golgi Apparatus/metabolism
- Humans
- Osteochondrodysplasias*/metabolism
- Protein Transport
- Qa-SNARE Proteins/genetics
- Qa-SNARE Proteins/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 37718532 Full text @ J. Bone Miner. Res.
Citation
Guillemyn, B., De Saffel, H., Bek, J.W., Tapaneeyaphan, P., De Clercq, A., Jarayseh, T., Debaenst, S., Willaert, A., De Rycke, R., Byers, P.H., Rosseel, T., Coucke, P., Blaumeiser, B., Syx, D., Malfait, F., Symoens, S. (2023) Syntaxin 18 Defects in Human and Zebrafish Unravel Key Roles in Early Cartilage and Bone Development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 38(11):1718-1730.
Abstract
SNARE proteins comprise a conserved protein family responsible for catalyzing membrane fusion during vesicle traffic. Syntaxin18 (STX18) is a poorly characterized endoplasmic reticulum (ER)-resident t-SNARE. Recently, together with TANGO1 and SLY1, its involvement was shown in ER to Golgi transport of collagen II during chondrogenesis. We report a fetus with a severe osteochondrodysplasia in whom we identified a homozygous substitution of the highly conserved p.Arg10 to Pro of STX18. CRISPR/Cas9-mediated Stx18 deficiency in zebrafish reveals a crucial role for Stx18 in cartilage and bone development. Furthermore, increased expression of multiple components of the Stx18 SNARE complex and of COPI and COPII proteins suggests that Stx18 deficiency impairs antero- and retrograde vesicular transport in the crispant stx18 zebrafish. Taken together, our studies highlight a new candidate gene for a recessive form of osteochondrodysplasia, thereby possibly broadening the SNAREopathy phenotypic spectrum and opening new doors toward future research avenues. © 2023 American Society for Bone and Mineral Research (ASBMR).
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping