Alternative titles; symbols
HGNC Approved Gene Symbol: MPP4
Cytogenetic location: 2q33.1 Genomic coordinates (GRCh38) : 2:201,644,874-201,698,644 (from NCBI)
By expression profiling of retina-specific ESTs and RT-PCR of retinal RNA, Stohr and Weber (2001) obtained a cDNA encoding MPP4. The predicted 637-amino acid MPP4 protein, which is 36% identical to MPP3 (601114) and 75% identical to its rat homolog, contains an N-terminal PDZ domain, a central SH3 motif, and a C-terminal guanylate kinase (GUK)-like domain typical of MAGUK (membrane-associated GUK) proteins. Northern blot and RT-PCR analyses detected a 3.8-kb transcript expressed only in retina. Stohr and Weber (2001) noted that tissue-restricted expression of a MAGUK protein had not been reported previously.
By immunofluorescence analysis of mouse retina, Yang et al. (2007) showed that Mpp4 localized to the synaptic layer of photoreceptors. Immunoelectron microscopy showed that Mpp4 distributed primarily along the plasma membrane of photoreceptor synaptic terminals.
By genomic sequence analysis, Stohr and Weber (2001) determined that the MPP4 gene contains 22 exons and spans at least 50 kb.
By BAC and sequence database analysis, Stohr and Weber (2001) mapped the MPP4 gene to chromosome 2q31. They proposed that MPP4 represents a candidate gene for retinal disease due to its colocalization with RP26, a locus for autosomal recessive retinitis pigmentosa (Bayes et al., 1998).
Aartsen et al. (2006) found that Mpp4 -/- mice were indistinguishable from wildtype littermates and that they grew and bred normally. However, histologic examination revealed sporadic photoreceptor displacement. Light and electron microscopy of Mpp4 -/- retinas revealed no structural differences at the outer limiting membrane or photoreceptor synapse. Electroretinography revealed overtly normal retinal activity, and scanning laser ophthalmology showed apparently normal overall structure in Mpp4 -/- retinas. Mpp4 -/- retinas showed downregulation of Psd95 (DLG4; 602887) and mislocalization of both Psd95 and Veli3 (LIN7C; 612332) at the photoreceptor presynaptic membrane. Aartsen et al. (2006) proposed that MPP4 may function as a recruitment factor to organize signal transducers at the photoreceptor synapse.
Yang et al. (2007) found that Mpp4 -/- mice were viable, fertile, and apparently healthy. However, Mpp4 -/- retinas showed abnormal sensitivity to light flash. Histologic examination revealed that the size, shape, and density of rod terminals and synaptic vesicles were normal, but the height of synaptic ribbons was increased in Mpp4 -/- mice under both dark- and light-adapted conditions, suggesting elevated Ca(2+) concentrations. Western blot analysis showed reduced expression of the rhodopsin (RHO; 180380)-deactivating proteins, rhodopsin kinase (GRK1; 180381) and recoverin (RCV1; 179618). Mpp4 -/- retina also showed increased expression of Serca2 (ATP2A2; 108740) and abnormal localization of type-2 inositol trisphosphate receptor (ITPR2; 600144), confirming altered Ca(2+) homeostasis. The retinal content of plasma membrane Ca(2+) ATPases (PMCAs; see 108731) was unchanged, but immunofluorescence analysis revealed that the localization of PMCAs at the rod presynaptic plasma membrane was lost. Yang et al. (2007) concluded that MPP4 has a role in the membrane localization of PMCAs and in modulating Ca(2+) homeostasis and synaptic transmission in rod photoreceptors.
Aartsen, W. M., Kantardzhieva, A., Klooster, J., van Rossum, A. G. S. H., van de Pavert, S. A., Versteeg, I., Cardozo, B. N., Tonagel, F., Beck, S. C., Tanimoto, N., Seeliger, M. W., Wijnholds, J. Mpp4 recruits Psd95 and Veli3 towards the photoreceptor synapse. Hum. Molec. Genet. 15: 1291-1302, 2006. [PubMed: 16520334] [Full Text: https://doi.org/10.1093/hmg/ddl047]
Bayes, M., Goldaracena, B., Martinez-Mir, A., Iragui-Madoz, M. I., Solans, T., Chivelet, P., Bussaglia, E., Ramos-Arroyo, M. A., Baiget, M., Vilageliu, L., Balcells, S., Gonzalez-Duarte, R., Grinberg, D. A new autosomal recessive retinitis pigmentosa locus maps on chromosome 2q31-q33. J. Med. Genet. 35: 141-145, 1998. [PubMed: 9507394] [Full Text: https://doi.org/10.1136/jmg.35.2.141]
Stohr, H., Weber, B. H. F. Cloning and characterization of the human retina-specific gene MPP4, a novel member of the p55 subfamily of MAGUK proteins. Genomics 74: 377-384, 2001. [PubMed: 11414766] [Full Text: https://doi.org/10.1006/geno.2001.6559]
Yang, J., Pawlyk, B., Wen, X.-H., Adamian, M., Soloviev, M., Michaud, N., Zhao, Y., Sandberg, M. A. Makino, C. L.; Li, T.: Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Hum. Molec. Genet. 16: 1017-1029, 2007. [PubMed: 17341488] [Full Text: https://doi.org/10.1093/hmg/ddm047]