Cornichon regulates transport and secretion of TGFα-related proteins in metazoan cells
2007
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 TGFα-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 TGFα 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 TGFα family proteins. Alterations of cornichon expression result in changes in transport, processing and secretion of TGFα proteins. In particular, increased cornichon expression retains TGFα 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 TGFα family proteins.
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