Ucmaa (Grp-2) is required for zebrafish skeletal development. Evidence for a functional role of its glutamate γ-carboxylation
- Authors
- Neacsu, C.D., Grosch, M., Tejada, M., Winterpacht, A., Paulsson, M., Wagener, R., and Tagariello, A.
- ID
- ZDB-PUB-110816-20
- Date
- 2011
- Source
- Matrix biology : journal of the International Society for Matrix Biology 30(7-8): 369-78 (Journal)
- Registered Authors
- Keywords
- UCMA, GRP, cartilage, zebrafish, vitamin K, glutamate γ-carboxylation
- MeSH Terms
-
- 1-Carboxyglutamic Acid/metabolism*
- Alternative Splicing
- Amino Acid Sequence
- Animals
- Cartilage/cytology
- Cartilage/embryology
- Cartilage/growth & development*
- Cartilage/metabolism
- Cloning, Molecular
- Collagen Type II/metabolism
- Computational Biology
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Embryonic Development/drug effects
- Fluorescent Antibody Technique
- Gene Expression Regulation, Developmental
- Gene Knockdown Techniques
- Larva
- Mice
- Molecular Sequence Data
- Notochord/cytology
- Notochord/drug effects
- Notochord/embryology
- Notochord/metabolism
- Phenotype
- Protein Isoforms/genetics
- Protein Isoforms/metabolism
- Proteins/genetics
- Proteins/metabolism
- Sequence Alignment
- Sequence Homology
- Staining and Labeling
- Time Factors
- Warfarin/pharmacology
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/growth & development*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 21839171 Full text @ Matrix Biol.
- CTD
- 21839171
UCMA (alternatively named GRP) is a novel member of the family of γ-carboxyglutamate (Gla) containing proteins that is mainly expressed in cartilage. We have used the zebrafish as a model organism to study UCMA function. Due to the whole genome duplication two Ucma genes are present in zebrafish, ucmaa and ucmab, located on chromosomes 25 and 4, respectively. UCMA gene structure, alternative splicing and protein sequence are highly conserved between mammals and zebrafish and Ucmaa and Ucmab are expressed in zebrafish skeletal tissues. Ucmaa is first detected in the notochord at 18 hpf and expression continues during notochord development. In addition, it is widely present in the developing craniofacial cartilage. In contrast, the weakly expressed Ucmab can be first detected at specific sites in the craniofacial cartilage at 96 hpf, but not in notochord. Knockdown of ucmaa leads to severe growth retardation and perturbance of skeletal development. The cartilage of the morphants has a decreased aggrecan and collagen II content. Similar malformations were observed when glutamate γ-carboxylation was inhibited by warfarin treatment, indicating that glutamate γ-carboxylation is crucial for Ucma function and pointing to a role of UCMA in the pathogenesis of “warfarin embryopathies” and other human skeletal diseases.