VIPL, a VIP36-like membrane protein with a putative function in the export of glycoproteins from the endoplasmic reticulum.
Subsets of glycoproteins are thought to require lectin-like membrane receptors for efficient export out of the endoplasmic reticulum (ER). To identify new members related to two previously characterized intracellular lectins ERGIC-53/p58 and VIP36, we carried out an extensive database search using the conserved carbohydrate recognition domain (CRD) as a search string. A gene, more closely related to VIP36 than to ERGIC-53/p58, and hence called VIPL (VIP36-Like), was identified. VIPL has been conserved through evolution from zebra fish to man. The 2.4-kb VIPL mRNA was widely expressed to varying levels in different tissues. Using an antiserum prepared against the CRD, the 32-kDa VIPL protein was detected in various cell lines. The single N-linked glycan of VIPL remained endoglycosidase H-sensitive during a 2-h pulse-chase, even when the protein was overexpressed or mutated to allow export to the plasma membrane. VIPL localized primarily to the ER and partly to the Golgi complex. Like VIP36, the cytoplasmic tail of VIPL terminates in the sequence KRFY, a motif characteristic for proteins recycling between the ER and ERGIC/cis-Golgi. Mutating the retrograde transport signal KR to AA resulted in transport of VIPL to the cell surface. Finally, knock-down of VIPL mRNA using siRNA significantly slowed down the secretion of two glycoproteins (M(R) 35 and 250 kDa) to the medium, suggesting that VIPL may also function as an ER export receptor.
Neve
Etienne P A
EP
Ludwig Institute for Cancer Research, Stockholm Branch, Karolinska Institutet, Box 240, SE-17177 Stockholm, Sweden.
Svensson
Kerstin
K
Fuxe
Jonas
J
Pettersson
Ralf F
RF
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics; D017124:Conserved Sequence; D030561:Databases, Nucleic Acid; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000502:physiology*; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000502:physiology*; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D016415:Sequence Alignment; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D006023:Glycoproteins; C084004:LMAN1 protein, human; C086797:LMAN2 protein, human; C477344:LMAN2L protein, human; D037102:Lectins; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase