title: Evidence for splice transcript variants of TMEM165, a gene involved in CDG.
abstract: Defects in TMEM165 gene cause a type-II Congenital Disorder of Glycosylation affecting Golgi glycosylation processes. TMEM165 patients exhibit psychomotor retardation, important osteoporosis, scoliosis, irregular epiphyses and thin bone cortex. TMEM165 protein is highly conserved in evolution and belongs to the family of UPF0016 membrane proteins which could be an unique group of Ca2+/H+antiporters regulating Ca2+and pH homeostasis and mainly localized in the Golgi apparatus.
  
  
  
  RT-PCR from human brain tissues revealed TMEM165 splice-transcript variants. mRNA expression was analyzed by RT-Q-PCR. Expression plasmids allowed us to visualize isoform proteins and their subcellular localization. Their functions on glycosylation were achieved by looking at the gel mobility of highly glycosylated proteins in cells overexpressing isoforms.
  
  
  
  In this study, we highlight, as previously shown for other ion channels, the existence of TMEM165 splice-transcripts isoforms, in particular the Short-Form (SF) and the Long-Form (LF) transcripts, leading to a 129 aa and 259 aa protein isoform, respectively. These proteins both localize in the endoplasmic reticulum and have different effects on glycosylation compared to the wild-type protein (324 aa). We also point out that the SF is expressed at low levels in all human cells and tissues checked, excepted in brain, and forms homodimer. The LF was only expressed in the temporal lobe of human brain.
  
  
  
  The finding of numerous splice variants could lead to a family of TMEM165 isoforms. This family of TMEM165 splice transcripts could participate in the fine regulation of TMEM165 isoforms' functions and localizations.
authors.affiliation: Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F 59000 Lille, France. Electronic address: marie-ange.recchi@univ-lille1.fr.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Krzewinski-Recchi
authors.affiliation: Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F 59000 Lille, France.
authors.forename: Sven
authors.initials: S
authors.lastname: Potelle
authors.affiliation: Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F 59000 Lille, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mir
authors.affiliation: Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F 59000 Lille, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Vicogne
authors.affiliation: Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F 59000 Lille, France.
authors.forename: Eudoxie
authors.initials: E
authors.lastname: Dulary
authors.affiliation: Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F 59000 Lille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Duvet
authors.affiliation: Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F 59000 Lille, France.
authors.forename: Willy
authors.initials: W
authors.lastname: Morelle
authors.affiliation: Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F 59000 Lille, France.
authors.forename: Geoffroy
authors.initials: G
authors.lastname: de Bettignies
authors.affiliation: Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F 59000 Lille, France.
authors.forename: François
authors.initials: F
authors.lastname: Foulquier
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D017920:Antiporters; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D027682:Cation Transport Proteins; D045744:Cell Line, Tumor; D018981:Congenital Disorders of Glycosylation / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006031:Glycosylation; D006056:Golgi Apparatus / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D017920:Antiporters; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C575014:TMEM165 protein, human; D002118:Calcium
keywords: Congenital Disorders of Glycosylation; Golgi; N-glycosylation; Splice-transcript-isoforms; TMEM165