PUBLICATION
Elucidation of the dimeric interplay of dual MRAP2 proteins in the zebrafish
- Authors
- Wang, M., Zhai, Y., Lu, L., Zhang, C., Li, N., Xue, S., Cheng, D., Fu, S., Liu, Q., Zhang, C.
- ID
- ZDB-PUB-210210-5
- Date
- 2021
- Source
- Journal of Cellular Physiology 236(9): 6472-6480 (Journal)
- Registered Authors
- Keywords
- MC4R, MRAP2, heterodimer, homodimer, zebrafish
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cyclic AMP/biosynthesis
- HEK293 Cells
- Humans
- Intracellular Signaling Peptides and Proteins/chemistry
- Intracellular Signaling Peptides and Proteins/metabolism*
- Protein Multimerization*
- Signal Transduction
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/metabolism*
- PubMed
- 33559170 Full text @ J. Cell. Physiol.
Citation
Wang, M., Zhai, Y., Lu, L., Zhang, C., Li, N., Xue, S., Cheng, D., Fu, S., Liu, Q., Zhang, C. (2021) Elucidation of the dimeric interplay of dual MRAP2 proteins in the zebrafish. Journal of Cellular Physiology. 236(9):6472-6480.
Abstract
The melanocortin receptor accessory protein 2 (MRAP2) plays an essential role in the regulation of metabolic homeostasis and deletion of which results in severe obesity syndrome in mice and human. Mammalian MRAP2 is recognized as an endogenous physiological mediator through the potentiation of the MC4R signaling in vivo. Two isoforms of MRAP2 are identified in zebrafish genome, zMRAP2a and zMRAP2b. However, the mechanism of assembling dual topology and the regulatory roles of each complex on the melanocortin cascades remains unclear. In this study, we showed the bidirectional homo- and hetero-dimeric topologies of two zebrafish MRAP2 isoforms on the plasma membrane. Orientation fixed chimeric proteins could affect the trafficking and pharmacological properties of zMC4R signaling. Reciprocal replacement of zMRAP2a and zMRAP2b proteins elucidated the major participation of the carboxyl terminal as the functional domain for modulating zMC4R signaling. Our findings revealed the complex and dynamic conformational regulation of dual zebrafish MRAP2 proteins in vitro.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping