Cornichon regulates transport and secretion of TGFalpha-related proteins in metazoan cells.
Cornichon proteins are structurally related transmembrane proteins that have been studied in and Drosophila and yeast. In Drosophila, Cornichon (Cni) is involved in embryo polarization by the TGFalpha-related Gurken. In yeast, the Cni-related Erv14 is required for axial budding. A cargo receptor function has been proposed for Erv14 and Cni. Four mammalian Cni-like sequences have been identified. We carried out parallel functional analyses of the human Cni ortholog CNIH and Drosophila Cni in the processing and presentation of TGFalpha family proteins. Human CNIH complements the loss of Erv14 in yeast. Human CNIH and Drosophila Cni are primarily localized in the endoplasmic reticulum and associate with immature TGFalpha family proteins. Alterations of cornichon expression result in changes in transport, processing and secretion of TGFalpha proteins. In particular, increased cornichon expression retains TGFalpha proteins in the endoplasmic reticulum, whereas cornichon is required for their transport and secretion. Thus, cornichon proteins represent a functionally conserved protein family that acts in the selective transport and maturation of TGFalpha family proteins.
Castro
Carolina Perez
CP
Department of Cell and Tissue Biology, Program in Cell Biology, University of California at San Francisco, San Francisco, CA 94143-0512, USA.
Piscopo
Denise
D
Nakagawa
Takatoshi
T
Derynck
Rik
R
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells / Q000166:cytology / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004527:Egg Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D021381:Protein Transport; D034741:RNA, Small Interfering; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000302:isolation & purification / Q000378:metabolism*
C118276:CNIH1 protein, human; D029721:Drosophila Proteins; D004527:Egg Proteins; C493590:Erv14 protein, S cerevisiae; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D029701:Saccharomyces cerevisiae Proteins; D016211:Transforming Growth Factor alpha; C485557:cni protein, Drosophila