title: The serologically defined colon cancer antigen-3 (SDCCAG3) is involved in the regulation of ciliogenesis.
abstract: A primary cilium is present on most eukaryotic cells and represents a specialized organelle dedicated to signal transduction and mechanosensing. Defects in cilia function are the cause for several human diseases called ciliopathies. The serologically defined colon cancer antigen-3 (SDCCAG3) is a recently described novel endosomal protein mainly localized at early and recycling endosomes and interacting with several components of membrane trafficking pathways. Here we describe localization of SDCCAG3 to the basal body of primary cilia. Furthermore, we demonstrate that decreased expression levels of SDCCAG3 correlate with decreased ciliary length and a reduced percentage of ciliated cells. We show that SDCCAG3 interacts with the intraflagellar transport protein 88 (IFT88), a crucial component of ciliogenesis and intraciliary transport. Mapping experiments revealed that the N-terminus of SDCCAG3 mediates this interaction by binding to a region within IFT88 comprising several tetratricopeptide (TRP) repeats. Finally, we demonstrate that SDCCAG3 is important for ciliary localization of the membrane protein Polycystin-2, a protein playing an important role in the formation of polycystic kidney disease, but not for Rab8 another ciliary protein. Together these data suggest a novel role for SDCCAG3 in ciliogenesis and in localization of cargo to primary cilia.
authors: Department of Biomedical Science &Centre of Membrane Interactions and Dynamics, University of Sheffield, S10 2TN Sheffield, UK.
authors: Fangyan
authors: F
authors: Yu
authors: Department of Biomedical Science &Centre of Membrane Interactions and Dynamics, University of Sheffield, S10 2TN Sheffield, UK.
authors: Shruti
authors: S
authors: Sharma
authors: Department of Biomedical Science &Centre of Membrane Interactions and Dynamics, University of Sheffield, S10 2TN Sheffield, UK.
authors: Agnieszka
authors: A
authors: Skowronek
authors: Department of Biomedical Science &Centre of Membrane Interactions and Dynamics, University of Sheffield, S10 2TN Sheffield, UK.
authors: Kai Sven
authors: KS
authors: Erdmann
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001665:Binding Sites; D002923:Cilia / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D000072417:Protein Domains; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins
chemical_list: D000951:Antigens, Neoplasm; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D050396:TRPP Cation Channels; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins; C510453:ENTR1 protein, human; C098623:IFT88 protein, human