CIN85 is localized at synapses and forms a complex with S-SCAM via dendrin.
Membrane-associated guanylate kinase inverted (MAGI)-1 plays a role as a scaffold at cell junctions in non-neuronal cells, while S-SCAM, its neuronal isoform, is involved in the organization of synapses. A search for MAGI-1-interacting proteins by yeast two-hybrid screening of a kidney cDNA library yielded dendrin. As dendrin was originally reported ... as a brain-specific postsynaptic protein, we tested the interaction between dendrin and S-SCAM and revealed that dendrin binds to the WW domains of S-SCAM. Dendrin is known to be dendritically translated but its function is largely unknown. To gain insights into the physiological meaning of the interaction, we performed a second yeast two-hybrid screening using dendrin as a bait. We identified CIN85, an endocytic scaffold protein, as a putative dendrin-interactor. Immunocytochemistry and subcellular fractionation analysis supported the synaptic localization of CIN85. The first SH3 domain and the C-terminal region of CIN85 bind to the proline-rich region and the N-terminal region of dendrin, respectively. In vitro experiments suggest that dendrin forms a ternary complex with CIN85 and S-SCAM and that this complex formation facilitates the recruitment of dendrin and S-SCAM to vesicle-like structures where CIN85 is accumulated.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Animals, Brain, Carrier Proteins, Guanylate Kinase, Humans, Intracellular Signaling Peptides and Proteins, Kidney, Membrane Proteins, Nerve Tissue Proteins, Protein Binding, Protein Structure, Tertiary, Rats, Signal Transduction, Synapses, Tissue Distribution, Two-Hybrid System Techniques
Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Animals, Brain, Carrier Proteins, Guanylate Kinase, Humans, Intracellular Signaling Peptides and Proteins, Kidney, Membrane Proteins, Nerve Tissue Proteins, Protein Binding, Protein Structure, Tertiary, Rats, Signal Transduction, Synapses, Tissue Distribution, Two-Hybrid System Techniques
J. Biochem.
Date: May. 01, 2006
PubMed ID: 16751601
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