Title : Interaction of serotonin 5-hydroxytryptamine type
2C receptors with PDZ10 of the
multi-PDZ domain
protein MUPP1
Abstract :
- By using the yeast two-hybrid system, we previously isolated a cDNA clone encoding a novel member of the multivalent PDZ protein family called MUPP1 containing 13 PDZ domains
- Here we report that the C terminus of the 5-hydroxytryptamine type 2C ( 5-HT(2C )) receptor selectively interacts with the 10th PDZ domain of MUPP1
- Mutations in the extreme C-terminal SSV sequence of the 5-HT(2C ) receptor confirmed that the SXV motif is critical for the interaction
- Co-immunoprecipitations of MUPP1 and 5-HT(2C ) receptors from transfected COS-7 cells and from rat choroid plexus verified this interaction in vivo
- Immunocytochemistry revealed an SXV motif-dependent co-clustering of both proteins in transfected COS-7 cells as well as a colocalization in rat choroid plexus
- A 5-HT(2C ) receptor-dependent unmasking of a C-terminal vesicular stomatitis virus epitope of MUPP1 suggests that the interaction triggers a conformational change within the MUPP1 protein
- Moreover, 5-HT(2A ) and 5-HT(2B ), sharing the C-terminal EX(V/I)SXV sequence with 5-HT(2C ) receptors , also bind MUPP1 PDZ domains in vitro
- The highest MUPP1 mRNA levels were found in all cerebral cortical layers, the hippocampus, the granular layer of the dentate gyrus, as well as the choroid plexus, where 5-HT(2C ) receptors are highly enriched
- We propose that MUPP1 may serve as a multivalent scaffold protein that selectively assembles and targets signaling complexes
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 1. MUPP1, domains
- 2. MUPP1, domain
- 2. receptor, terminus
- 3. receptor, sequence
- 6. MUPP1, epitope
- 7. MUPP1, domains
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):