title: The cytoplasmic/transmembrane domain of dipeptidyl peptidase IV, a type II glycoprotein, contains an apical targeting signal that does not specifically interact with lipid rafts.
abstract: We investigated the signals involved in the apical targeting of dipeptidyl peptidase IV (DPP IV/CD26), an archetypal type II transmembrane glycoprotein. A secretory construct, corresponding to the DPP IV ectodomain, was first stably expressed in both the enterocytic-like cell line Caco-2 and the epithelial kidney MDCK cells. Most of the secretory form of the protein was delivered apically in MDCK cells, whereas secretion was 60% basolateral in Caco-2 cells, indicating that DPP IV ectodomain targeting is cell-type-dependent. A chimera (CTM-GFP) containing only the cytoplasmic and transmembrane domains of mouse DPP IV plus the green fluorescent protein was then studied. In both cell lines, this chimera was preferentially expressed at the apical membrane. By contrast, a secretory form of GFP was randomly secreted, indicating that GFP by itself does not contain cryptic targeting information. Comparison of the sequence of the transmembrane domain of DPP IV and several other apically targeted proteins does not show any consensus, suggesting that the apical targeting signal may be conformational. Neither the DPP IV nor the CTM-GFP chimera was enriched in lipid rafts. Together these results indicate that, besides the well-known raft-dependent apical targeting pathway, the fate of the CTM domain of DPP IV may reveal a new raft-independent apical pathway.
authors.affiliation: INSERM U538, CHU St Antoine, 27 rue Chaligny, Paris Cedex 12, 75571, France.
authors.forename: T A
authors.initials: TA
authors.lastname: Slimane
authors.forename: C
authors.initials: C
authors.lastname: Lenoir
authors.forename: V
authors.initials: V
authors.lastname: Bello
authors.forename: J L
authors.initials: JL
authors.lastname: Delaunay
authors.forename: J W
authors.initials: JW
authors.lastname: Goding
authors.forename: S
authors.initials: S
authors.lastname: Chwetzoff
authors.forename: M
authors.initials: M
authors.lastname: Maurice
authors.forename: J A
authors.initials: JA
authors.lastname: Fransen
authors.forename: G
authors.initials: G
authors.lastname: Trugnan
mesh_terms: D000818:Animals; D001665:Binding Sites; D018938:Caco-2 Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004285:Dogs; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D021382:Protein Sorting Signals; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D018819:Dipeptidyl Peptidase 4