title: Cytosolic N-terminal arginine-based signals together with a luminal signal target a type II membrane protein to the plant ER.
abstract: BACKGROUND
  In eukaryotic cells, the membrane compartments that constitute the exocytic pathway are traversed by a constant flow of lipids and proteins. This is particularly true for the endoplasmic reticulum (ER), the main "gateway of the secretory pathway", where biosynthesis of sterols, lipids, membrane-bound and soluble proteins, and glycoproteins occurs. Maintenance of the resident proteins in this compartment implies they have to be distinguished from the secretory cargo. To this end, they must possess specific ER localization determinants to prevent their exit from the ER, and/or to interact with receptors responsible for their retrieval from the Golgi apparatus. Very few information is available about the signal(s) involved in the retention of membrane type II protein in the ER but it is generally accepted that sorting of ER type II cargo membrane proteins depends on motifs mainly located in their cytosolic tails.
  
  
  RESULTS
  Here, using Arabidopsis glucosidase I as a model, we have identified two types of signals sufficient for the location of a type II membrane protein in the ER. A first signal is located in the luminal domain, while a second signal corresponds to a short amino acid sequence located in the cytosolic tail of the membrane protein. The cytosolic tail contains at its N-terminal end four arginine residues constitutive of three di-arginine motifs (RR, RXR or RXXR) independently sufficient to confer ER localization. Interestingly, when only one di-arginine motif is present, fusion proteins are located both in the ER and in mobile punctate structures, distinct but close to Golgi bodies. Soluble and membrane ER protein markers are excluded from these punctate structures, which also do not colocalize with an ER-exit-site marker. It is hypothesized they correspond to sites involved in Golgi to ER retrotransport.
  
  
  CONCLUSIONS
  Altogether, these results clearly show that cytosolic and luminal signals responsible for ER retention could coexist in a same type II membrane protein. These data also suggest that both retrieval and retention mechanisms govern protein residency in the ER membrane. We hypothesized that mobile punctate structures not yet described at the ER/Golgi interface and tentatively named GERES, could be involved in retrieval mechanisms from the Golgi to the ER.
authors.affiliation: Laboratoire GLYCAD, IFRMP 23, Université de Rouen, 76821 Mont Saint Aignan Cedex, France. aboulaflous@gmail.com
authors.forename: Aurélia
authors.initials: A
authors.lastname: Boulaflous
authors.forename: Claude
authors.initials: C
authors.lastname: Saint-Jore-Dupas
authors.forename: Marie-Carmen
authors.initials: MC
authors.lastname: Herranz-Gordo
authors.forename: Sophie
authors.initials: S
authors.lastname: Pagny-Salehabadi
authors.forename: Carole
authors.initials: C
authors.lastname: Plasson
authors.forename: Frédéric
authors.initials: F
authors.lastname: Garidou
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Kiefer-Meyer
authors.forename: Christophe
authors.initials: C
authors.lastname: Ritzenthaler
authors.forename: Loïc
authors.initials: L
authors.lastname: Faye
authors.forename: Véronique
authors.initials: V
authors.lastname: Gomord
mesh_terms: D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D030821:Plants, Genetically Modified / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014026:Nicotiana / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C042059:glucosidase I; D000520:alpha-Glucosidases