Characterization of MPP4, a gene highly expressed in photoreceptor cells, and mutation analysis in retinitis pigmentosa.
Membrane-associated guanylate kinase (MAGUK) proteins are cell-cell contact organizing molecules that mediate targeting, clustering and anchoring of proteins at synapses and other cell junctions. MAGUK proteins may contain multiple protein-protein interaction motifs including PDZ, SH3 and guanylate kinase (GuK) domains. In this study, we performed a detailed analysis of the expression pattern of MPP4, a recently described member of the MAGUK protein family. We confirmed that this gene is highly expressed in retina, and demonstrate that it is also present, at lower levels, in brain. We identified a new retina specific isoform encoding a predicted protein lacking 71 amino acids. This protein region contains a newly identified L27 domain, another module playing a role in protein-protein interaction. By RNA in situ hybridization, Mpp4 expression was found to be localized to photoreceptor cells in postnatal retina. The MPP4 gene is localized to chromosome 2, in band 2q31-33, where a locus for autosomal recessive retinitis pigmentosa (RP26) has been mapped. Mutation analysis of the entire open reading frame of the MPP4 gene in a RP26 family revealed no pathologic mutations. In addition, we did not identify mutations in a panel of 300 unrelated patients with retinitis pigmentosa.
Conte
Ivan
I
Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80129, Naples, Italy.
Lestingi
Marta
M
den Hollander
Anneke
A
Miano
Maria Giuseppina
MG
Alfano
Giovanna
G
Circolo
Diego
D
Pugliese
Mariarosaria
M
Testa
Francesco
F
Simonelli
Francesca
F
Rinaldi
Ernesto
E
Baiget
Montserrat
M
Banfi
Sandro
S
Ciccodicola
Alfredo
A
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D005136:Eye Proteins; D015971:Gene Expression Regulation, Enzymologic; D051528:Guanylate Kinases; D006801:Humans; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics*; D010786:Photoreceptor Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000201:enzymology / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D005136:Eye Proteins; D008565:Membrane Proteins; D012313:RNA; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C470950:MPP4 protein, human