title: Synergistic interaction of tubby and tubby-like protein 1 (Tulp1).
abstract: Mutations in either tubby or tubby-like protein 1 (Tulp1) cause retinal degeneration with undefined mechanisms. We recently identified both proteins with unconventional secretion as novel MerTK-specific phagocytosis ligands for retinal pigment epithelium (RPE) cells. Using our newly-developed open reading frame (ORF) phage display as a technology for protein-protein interactions, we identified Tulp1 as a Tubby-binding protein. The interaction of tubby and Tulp1 was verified by yeast two-hybrid and protein pull-down assays. Tubby and Tulp1 form heterodimer or heterooligomer and their interaction was functionally revealed by their synergistic stimulation of RPE phagocytosis. Tubby and Tulp1 mediated phagocytosis through MerTK-dependent signaling with non-muscle myosin II redistribution leading to colocalization of phagocytosed vesicles with rearranged NMMIIA.
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, 89154, Las Vegas, NV, USA, nora.caberoy@unlv.edu.
authors.forename: Nora Blanca
authors.initials: NB
authors.lastname: Caberoy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002460:Cell Line; D019281:Dimerization; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D024462:Myosin Type II / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D000076202:c-Mer Tyrosine Kinase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C508878:TUB protein, human; C105443:TULP1 protein, human; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D024462:Myosin Type II