title: TM9 family proteins control surface targeting of glycine-rich transmembrane domains.
abstract: TM9 family proteins (also named Phg1 proteins) have been previously shown to control cell adhesion by determining the cell surface localization of adhesion proteins such as the Dictyostelium SibA protein. Here, we show that the glycine-rich transmembrane domain (TMD) of SibA is sufficient to confer Phg1A-dependent surface targeting to a reporter protein. Accordingly, in Dictyostelium phg1A-knockout (KO) cells, proteins with glycine-rich TMDs were less efficiently transported out of the endoplasmic reticulum (ER) and to the cell surface. Phg1A, as well as its human ortholog TM9SF4 specifically associated with glycine-rich TMDs. In human cells, genetic inactivation of TM9SF4 resulted in an increased retention of glycine-rich TMDs in the endoplasmic reticulum, whereas TM9SF4 overexpression enhanced their surface localization. The bulk of the TM9SF4 protein was localized in the Golgi complex and a proximity-ligation assay suggested that it might interact with glycine-rich TMDs. Taken together, these results suggest that one of the main roles of TM9 proteins is to serve as intramembrane cargo receptors controlling exocytosis and surface localization of a subset of membrane proteins.
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva 4 CH-1211, Switzerland.
authors.forename: Jackie
authors.initials: J
authors.lastname: Perrin
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva 4 CH-1211, Switzerland.
authors.forename: Marion
authors.initials: M
authors.lastname: Le Coadic
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva 4 CH-1211, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vernay
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva 4 CH-1211, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Dias
authors.affiliation: Department of Biochemistry, Sciences II, University of Geneva, 30 quai Ernest-Ansermet, Geneva 4 CH-1211, Switzerland.
authors.forename: Navin
authors.initials: N
authors.lastname: Gopaldass
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva 4 CH-1211, Switzerland.
authors.forename: Hajer
authors.initials: H
authors.lastname: Ouertatani-Sakouhi
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva 4 CH-1211, Switzerland Pierre.Cosson@unige.ch.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cosson
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D004023:Dictyostelium; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D005998:Glycine
keywords: Phg1; Secretory pathway; Sorting; TM9 protein; Transmembrane domain