Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Biological Assay
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Brain-Derived Neurotrophic Factor / metabolism
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Brain-Derived Neurotrophic Factor / pharmacology
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Adhesion / genetics
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Cell Movement / drug effects
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Cell Movement / physiology*
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Cells, Cultured
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Chemokine CXCL12
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Chemokines, CXC / metabolism
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Chemokines, CXC / pharmacology
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Chemotactic Factors / metabolism*
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Chemotactic Factors / pharmacology
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Cytoplasm / metabolism
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Ephrin-B1
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Ephrin-B2
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GTP-Binding Proteins*
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GTPase-Activating Proteins*
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Heterotrimeric GTP-Binding Proteins / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Molecular Sequence Data
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism
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Protein Structure, Tertiary / physiology
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RGS Proteins
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Sequence Homology, Amino Acid
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Transfection
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Two-Hybrid System Techniques
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Xenopus
Substances
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Brain-Derived Neurotrophic Factor
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Carrier Proteins
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Chemokine CXCL12
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Chemokines, CXC
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Chemotactic Factors
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Cxcl12 protein, mouse
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Ephrin-B1
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Ephrin-B2
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GTPase-Activating Proteins
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Membrane Proteins
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RGS Proteins
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Rgs3 protein, mouse
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GTP-Binding Proteins
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Heterotrimeric GTP-Binding Proteins