title: CASP, the alternatively spliced product of the gene encoding the CCAAT-displacement protein transcription factor, is a Golgi membrane protein related to giantin.
abstract: Large coiled-coil proteins are being found in increasing numbers on the membranes of the Golgi apparatus and have been proposed to function in tethering of transport vesicles and in the organization of the Golgi stack. Members of one class of Golgi coiled-coil protein, comprising giantin and golgin-84, are anchored to the bilayer by a single C-terminal transmembrane domain (TMD). In this article, we report the characterization of another mammalian coiled-coil protein, CASP, that was originally identified as an alternatively spliced product of the CUTL1 gene that encodes CCAAT-displacement protein (CDP), the human homologue of the Drosophila homeodomain protein Cut. We find that the Caenorhabditis elegans homologues of CDP and CASP are also generated from a single gene. CASP lacks the DNA binding motifs of CDP and was previously reported to be a nuclear protein. Herein, we show that it is in fact a Golgi protein with a C-terminal TMD and shares with giantin and golgin-84 a conserved histidine in its TMD. However, unlike these proteins, CASP has a homologue in Saccharomyces cerevisiae, which we call COY1. Deletion of COY1 does not affect viability, but strikingly restores normal growth to cells lacking the Golgi soluble N-ethylmaleimide-sensitive factor attachment protein receptor Gos1p. The conserved histidine is necessary for Coy1p's activity in cells lacking Gos1p, suggesting that the TMD of these transmembrane Golgi coiled-coil proteins is directly involved in their function.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom.
authors.forename: Alison K
authors.initials: AK
authors.lastname: Gillingham
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Pfeifer
authors.forename: Sean
authors.initials: S
authors.lastname: Munro
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000737:chemistry* / Q000378:metabolism; D000077614:Golgi Matrix Proteins; D018398:Homeodomain Proteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016366:Open Reading Frames; D011485:Protein Binding; D050766:Qb-SNARE Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D050600:SNARE Proteins; D012441:Saccharomyces cerevisiae / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C080632:CUX1 protein, human; C490973:GOS1 protein, S cerevisiae; C490972:GOSR1 protein, human; D000077614:Golgi Matrix Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D050766:Qb-SNARE Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C087574:macrogolgin