Yan Shan Ong1,#, Ton Hoai Thi Tran1,#, Natalia V Gounko1,2 and Wanjin Hong1,3,*.
1 Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore
2 IMB-IMCB Joint Electron Microscopy Suite, 20 Biopolis Street, Singapore 138671, Singapore
3 Department of Biochemistry, National University of Singapore, Singapore.
# Yan Shan Ong and Ton Hoai Thi Tran contributed equally to this work.
* Corresponding author
Published online in Journal of Cell Science on 7 May 2014.
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 apparatus. Biochemical and cell biological analysis suggests that TMEM115 has 4 candidate transmembrane domains located at the N-terminal region. Both the N- and C-terminal domains are oriented towards the cytoplasm. Immunofluoresence 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 COG complex. Co-immunoprecipitation and in vitro binding experiments reveals that TMEM115 interacts with COG complex, and may self-interact to form dimers or oligomers. A short region (residues 206-229) immediately to the C-terminal side of the 4th transmembrane domain is both necessary and sufficient for Golgi targeting. Knockdown of TMEM115 also reduces the binding of lectins PNA and HPA, suggesting an altered O-linked glycosylation profile. These results establish that TMEM115 is a novel integral membrane protein of the Golgi stack regulating Golgi-ER retrograde transport and is likely part of the machinery of the COG complex.
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