PUBLICATION
The interaction of nucleoside diphosphate kinase B with Gbetagamma dimers controls heterotrimeric G protein function
- Authors
- Hippe, H.J., Wolf, N.M., Abu-Taha, I., Mehringer, R., Just, S., Lutz, S., Niroomand, F., Postel, E.H., Katus, H.A., Rottbauer, W., and Wieland, T.
- ID
- ZDB-PUB-091023-23
- Date
- 2009
- Source
- Proceedings of the National Academy of Sciences of the United States of America 106(38): 16269-16274 (Journal)
- Registered Authors
- Just, Steffen, Rottbauer, Wolfgang, Wolf, Nadine
- Keywords
- cAMP, cardiac contractility, G proteins, NDPK, zebrafish
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cells, Cultured
- Cyclic AMP/metabolism
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Fibroblasts/cytology
- Fibroblasts/metabolism
- GTP-Binding Protein beta Subunits/chemistry
- GTP-Binding Protein beta Subunits/genetics
- GTP-Binding Protein beta Subunits/metabolism*
- GTP-Binding Protein gamma Subunits/chemistry
- GTP-Binding Protein gamma Subunits/genetics
- GTP-Binding Protein gamma Subunits/metabolism*
- Gene Expression Regulation, Developmental
- Gene Knockdown Techniques
- Heterotrimeric GTP-Binding Proteins/genetics
- Heterotrimeric GTP-Binding Proteins/metabolism*
- Heterotrimeric GTP-Binding Proteins/physiology
- Humans
- Immunoblotting
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Molecular Sequence Data
- Myocardial Contraction/genetics
- Myocardial Contraction/physiology
- Myocardium/metabolism
- NM23 Nucleoside Diphosphate Kinases/genetics
- NM23 Nucleoside Diphosphate Kinases/metabolism*
- Protein Binding
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Homology, Amino Acid
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 19805292 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Hippe, H.J., Wolf, N.M., Abu-Taha, I., Mehringer, R., Just, S., Lutz, S., Niroomand, F., Postel, E.H., Katus, H.A., Rottbauer, W., and Wieland, T. (2009) The interaction of nucleoside diphosphate kinase B with Gbetagamma dimers controls heterotrimeric G protein function. Proceedings of the National Academy of Sciences of the United States of America. 106(38):16269-16274.
Abstract
Heterotrimeric G proteins in physiological and pathological processes have been extensively studied so far. However, little is known about mechanisms regulating the cellular content and compartmentalization of G proteins. Here, we show that the association of nucleoside diphosphate kinase B (NDPK B) with the G protein betagamma dimer (Gbetagamma) is required for G protein function in vivo. In zebrafish embryos, morpholino-mediated knockdown of zebrafish NDPK B, but not NDPK A, results in a severe decrease in cardiac contractility. The depletion of NDPK B is associated with a drastic reduction in Gbeta(1)gamma(2) dimer expression. Moreover, the protein levels of the adenylyl cyclase (AC)-regulating Galpha(s) and Galpha(i) subunits as well as the caveolae scaffold proteins caveolin-1 and -3 are strongly reduced. In addition, the knockdown of the zebrafish Gbeta(1) orthologs, Gbeta(1) and Gbeta(1like), causes a cardiac phenotype very similar to that of NDPK B morphants. The loss of Gbeta(1)/Gbeta(1like) is associated with a down-regulation in caveolins, AC-regulating Galpha-subunits, and most important, NDPK B. A comparison of embryonic fibroblasts from wild-type and NDPK A/B knockout mice demonstrate a similar reduction of G protein, caveolin-1 and basal cAMP content in mammalian cells that can be rescued by re-expression of human NDPK B. Thus, our results suggest a role for the interaction of NDPK B with Gbetagamma dimers and caveolins in regulating membranous G protein content and maintaining normal G protein function in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping