Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction.

Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print Cited Medium: Print ISSN: 0092-8674 (Print) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE

Publication: Cambridge, Ma : Cell Press
Original Publication: Cambridge, MIT Press.

GTP-Binding Proteins* ; GTPase-Activating Proteins*; Carrier Proteins/*metabolism ; Cell Movement/*physiology ; Chemotactic Factors/*metabolism ; Heterotrimeric GTP-Binding Proteins/*metabolism ; Membrane Proteins/*metabolism ; Signal Transduction/*physiology; Animals ; Biological Assay ; Brain-Derived Neurotrophic Factor/metabolism ; Brain-Derived Neurotrophic Factor/pharmacology ; Carrier Proteins/genetics ; Cell Adhesion/genetics ; Cell Movement/drug effects ; Cells, Cultured ; Chemokine CXCL12 ; Chemokines, CXC/metabolism ; Chemokines, CXC/pharmacology ; Chemotactic Factors/pharmacology ; Cytoplasm/metabolism ; Ephrin-B1 ; Ephrin-B2 ; Membrane Proteins/genetics ; Mice ; Molecular Sequence Data ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Protein Structure, Tertiary/physiology ; RGS Proteins ; Sequence Homology, Amino Acid ; Signal Transduction/drug effects ; Transfection ; Two-Hybrid System Techniques ; Xenopus

Transmembrane B ephrins and their Eph receptors signal bidirectionally. However, neither the cell biological effects nor signal transduction mechanisms of the reverse signal are well understood. We describe a cytoplasmic protein, PDZ-RGS3, which binds B ephrins through a PDZ domain, and has a regulator of heterotrimeric G protein signaling (RGS) domain. PDZ-RGS3 can mediate signaling from the ephrin-B cytoplasmic tail. SDF-1, a chemokine with a G protein-coupled receptor, or BDNF, act as chemoattractants for cerebellar granule cells, with SDF-1 action being selectively inhibited by soluble EphB receptor. This study reveals a pathway that links reverse signaling to cellular guidance, uncovers a novel mode of control for G proteins, and demonstrates a mechanism for selective regulation of responsiveness to neuronal guidance cues.

HD29417 United States HD NICHD NIH HHS; NS40043 United States NS NINDS NIH HHS

GENBANK AF350047

0 (Brain-Derived Neurotrophic Factor)
0 (Carrier Proteins)
0 (Chemokine CXCL12)
0 (Chemokines, CXC)
0 (Chemotactic Factors)
0 (Cxcl12 protein, mouse)
0 (Ephrin-B1)
0 (Ephrin-B2)
0 (GTPase-Activating Proteins)
0 (Membrane Proteins)
0 (RGS Proteins)
0 (Rgs3 protein, mouse)
EC 3.6.1.- (GTP-Binding Proteins)
EC 3.6.5.1 (Heterotrimeric GTP-Binding Proteins)

Date Created: 20010413 Date Completed: 20010517 Latest Revision: 20220224

20221213

10.1016/s0092-8674(01)00297-5

11301003