title: Dynamics of the rhomboid-like protein RHBDD2 expression in mouse retina and involvement of its human ortholog in retinitis pigmentosa.
abstract: The novel rhomboid-like protein RHBDD2 is distantly related to rhomboid proteins, a group of highly specialized membrane-bound proteases that catalyze regulated intramembrane proteolysis. In retina, RHBDD2 is expressed from embryonic stages to adulthood, and its levels show age-dependent changes. RHBDD2 is distinctly abundant in the perinuclear region of cells, and it localizes to their Golgi. A glycine zipper motif present in one of the transmembrane domains of RHBDD2 is important for its packing into the Golgi membranes. Its deletion causes dislodgment of RHBDD2 from the Golgi. A specific antibody against RHBDD2 recognizes two forms of the protein, one with low (39 kDa; RHBDD2(L)) and the other with high (117 kDa; RHBDD2H) molecular masses in mouse retinal extracts. RHBDD2(L) seems to be ubiquitously expressed in all retinal cells. In contrast, RHBDD2H seems to be present only in the outer segments of cone photoreceptors and may correspond to a homotrimer of RHBDD2(L). This protein consistently co-localizes with S- and M-types of cone opsins. We identified a homozygous mutation in the human RHBDD2 gene, R85H, that co-segregates with disease in affected members of a family with autosomal recessive retinitis pigmentosa. Our findings suggest that the RHBDD2 protein plays important roles in the development and normal function of the retina.
authors: Jules Stein Eye Institute, UCLA, Los Angeles, California 90095. Electronic address: akhmedov@jsei.ucla.edu.
authors: Novruz B
authors: NB
authors: Ahmedli
authors: Jules Stein Eye Institute, UCLA, Los Angeles, California 90095.
authors: Yekaterina
authors: Y
authors: Gribanova
authors: Jules Stein Eye Institute, UCLA, Los Angeles, California 90095.
authors: Collins C
authors: CC
authors: Njoku
authors: Jules Stein Eye Institute, UCLA, Los Angeles, California 90095.
authors: Akash
authors: A
authors: Naidu
authors: Jules Stein Eye Institute, UCLA, Los Angeles, California 90095.
authors: Alejandra
authors: A
authors: Young
authors: Jules Stein Eye Institute, UCLA, Los Angeles, California 90095.
authors: Emmanuel
authors: E
authors: Mendoza
authors: Jules Stein Eye Institute, UCLA, Los Angeles, California 90095.
authors: Clyde K
authors: CK
authors: Yamashita
authors: Department of Molecular Biology, Hacettepe University, 06230 Beytepe-Ankara, Turkey.
authors: Riza Köksal
authors: RK
authors: Özgül
authors: Department of Natural Sciences, University of Houston-Downtown, Houston, Texas 77002.
authors: Jerry E
authors: JE
authors: Johnson
authors: College of Optometry, University of Houston, Houston, Texas 77004; Department of Biology and Biochemistry, University of Houston, Houston, Texas 77004; Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, Texas 77004.
authors: Donald A
authors: DA
authors: Fox
authors: Jules Stein Eye Institute, UCLA, Los Angeles, California 90095; Molecular Biology Institute, UCLA, Los Angeles, California 90095; Brain Research Institute, UCLA, Los Angeles, California 90095.
authors: Debora B
authors: DB
authors: Farber
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D010450:Endopeptidases / Q000096:biosynthesis* / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D005998:Glycine / Q000737:chemistry; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000502:physiology*; D055355:Opsins / Q000737:chemistry; D011247:Pregnancy; D011270:Pregnancy, Animal; D012160:Retina / Q000196:embryology / Q000378:metabolism*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D055355:Opsins; C544929:RHBDD2 protein, human; C581322:RHBDD2 protein, mouse; D010450:Endopeptidases; D005998:Glycine
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