Disease relevance of Mpdz

• Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1 [1].
• With regard to the consequences of these interactions in cells, we showed that Ad9 E4-ORF1 aberrantly sequesters MUPP1 within the cytoplasm of cells whereas HPV-18 E6 targets this cellular protein for degradation [2].
• The coxsackievirus and adenovirus receptor interacts with the multi-PDZ domain protein-1 (MUPP-1) within the tight junction [3].

Psychiatry related information on Mpdz

• Our findings provide a framework to define the protein interactions and neural circuit by which this gene's product (multiple PDZ domain protein) affects drug dependence, withdrawal and relapse [4].

High impact information on Mpdz

• CAR and MUPP1 were found to colocalize at the tight junction, to coprecipitate from epithelial cells, and to interact in vitro [3].
• To investigate whether phosphorylation of these serines in the receptor regulates MUPP1 interaction, we used several approaches [5].
• Alkaline phosphatase treatment reverses the effect of serotonin, indicating that agonist-induced phosphorylation at Ser458 resulted in a loss of MUPP1 association and also revealed a significant amount of basal phosphorylation of the receptor [5].
• Furthermore, in vitro binding and transfection experiments showed that junctional adhesion molecule, another TJ adhesion molecule, also bound to the PDZ9 domain of MUPP1 [6].
• The results of the present study suggest that TAPP1 and TAPP2 could function in cells as adapter proteins to recruit MUPP1, or other proteins that they may interact with, to the plasma membrane in response to signals that elevate PtdIns(3,4)P2 [7].

Biological context of Mpdz

• To date, Mpdz, which encodes the multiple PSD95/DLG/ZO-1 (PDZ) domain protein (MPDZ), is the only gene within the interval shown to have allelic variants that differ in coding sequence and/or expression, making it a strong candidate gene for the QTL [8].
• Congenic mapping of alcohol and pentobarbital withdrawal liability loci to a <1 centimorgan interval of murine chromosome 4: identification of Mpdz as a candidate gene [9].
• Previous work indicates that Mpdz haplotypes in standard mouse strains encode distinct protein variants (MPDZ1-3), and that MPDZ status is genetically correlated with severity of withdrawal from alcohol and pentobarbital [8].
• Our results provide evidence that Mpdz may have pleiotropic effects on multiple seizure phenotypes, including seizures associated with withdrawal from two classes of central nervous system (CNS) depressants and sensitivity to specific chemiconvulsants that affect glutaminergic and GABAergic neurotransmission [8].

Anatomical context of Mpdz

• Immunofluorescence confocal microscopy as well as immunoelectron microscopy with this antibody revealed that in polarized epithelial cells MUPP1 was exclusively concentrated at TJs [6].
• Our results indicate that MUPP1 immunoreactivity co-localizes with 5-HT(2A) or 5-HT(2C) receptor expression in all regions of the mouse brain, including the choroid plexus where 5-HT(2C) receptors are highly enriched [10].
• The inhibition of CAR expression with small interfering RNA inhibited MUPP1 localization to the tight junction [3].

Associations of Mpdz with chemical compounds

• Deletion of V967 of c-Kit abolished binding to MUPP-1 and drastically reduced its tyrosine kinase activity, suggesting that the structure of the C-terminal tail of c-Kit influences its enzymatic activity [11].
• Osmotic initiators of MUPP1 expression included NaCl, sucrose, mannitol, sodium acetate, and choline chloride but not urea [12].

Analytical, diagnostic and therapeutic context of Mpdz

• Sequence analysis of 15 standard inbred mouse strains identifies six Mpdz haplotypes that predict three MPDZ protein variants [9].
• We now report the generation and characterization of two independent MUPP1 antisera, which recognise distinct areas of the mouse brain in agreement with previous in-situ hybridization studies [10].
• We demonstrate that immunoprecipitation of endogenously expressed TAPP1 from 293-cell lysates results in the co-immunoprecipitation of endogenous MUPP1, indicating that these proteins are likely to interact with each other physiologically [7].

References