title: TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport.
abstract: Searching and evaluating the Human Protein Atlas for transmembrane proteins enabled us to identify an integral membrane protein, TMEM115, that is enriched in the Golgi complex. Biochemical and cell biological analysis suggested that TMEM115 has four candidate transmembrane domains located in the N-terminal region. Both the N- and C-terminal domains are oriented towards the cytoplasm. Immunofluorescence analysis supports that TMEM115 is enriched in the Golgi cisternae. Functionally, TMEM115 knockdown or overexpression delays Brefeldin-A-induced Golgi-to-ER retrograde transport, phenocopying cells with mutations or silencing of the conserved oligomeric Golgi (COG) complex. Co-immunoprecipitation and in vitro binding experiments reveals that TMEM115 interacts with the COG complex, and might self-interact to form dimers or oligomers. A short region (residues 206-229) immediately to the C-terminal side of the fourth transmembrane domain is both necessary and sufficient for Golgi targeting. Knockdown of TMEM115 also reduces the binding of the lectins peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA), suggesting an altered O-linked glycosylation profile. These results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex.
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
authors.forename: Yan Shan
authors.initials: YS
authors.lastname: Ong
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
authors.forename: Ton Hoai Thi
authors.initials: TH
authors.lastname: Tran
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore IMB-IMCB Joint Electron Microscopy Suite, 20 Biopolis Street, Singapore 138671, Singapore.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Gounko
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore Department of Biochemistry, National University of Singapore, Singapore 117599, Singapore mcbhwj@imcb.a-star.edu.sg.
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
mesh_terms: D000818:Animals; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C526513:TMEM115 protein, human; D033921:Vesicular Transport Proteins
keywords: COG complex; Golgi complex; Retrograde transport; TMEM115