Drosophila Cornichon acts as cargo receptor for ER export of the TGFalpha-like growth factor Gurken.
Drosophila Cornichon (Cni) is the founding member of a conserved protein family that also includes Erv14p, an integral component of the COPII-coated vesicles that mediate cargo export from the yeast endoplasmic reticulum (ER). During Drosophila oogenesis, Cni is required for transport of the TGFalpha growth factor Gurken (Grk) to the oocyte surface. Here, we show that Cni, but not the second Drosophila Cni homologue Cni-related (Cnir), binds to the extracellular domain of Grk, and propose that Cni acts as a cargo receptor recruiting Grk into COPII vesicles. Consequently, in the absence of Cni function, Grk fails to leave the oocyte ER. Proteolytic processing of Grk still occurs in cni mutant ovaries, demonstrating that release of the active growth factor from its transmembrane precursor occurs earlier during secretory transport than described for the other Drosophila TGFalpha homologues. Massive overexpression of Grk in a cni mutant background can overcome the requirement of Grk signalling for cni activity, confirming that cni is not essential for the production of the functional Grk ligand. However, the rescued egg chambers lack dorsoventral polarity. This demonstrates that the generation of temporally and spatially precisely coordinated Grk signals cannot be achieved by bulk flow secretion, but instead has to rely on fast and efficient ER export through cargo receptor-mediated recruitment of Grk into the secretory pathway.
Bökel
Christian
C
Max-Planck-Institut für molekulare Zellbiologie und Genetik, Dresden, Germany.
Dass
Sajith
S
Wilsch-Bräuninger
Michaela
M
Roth
Siegfried
S
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D022181:COP-Coated Vesicles / Q000378:metabolism; D029721:Drosophila Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004527:Egg Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008565:Membrane Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology / Q000648:ultrastructure; D009866:Oogenesis / Q000502:physiology; D010802:Phylogeny; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes
D029721:Drosophila Proteins; D004527:Egg Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D016211:Transforming Growth Factor alpha; C485557:cni protein, Drosophila; C083730:grk protein, Drosophila; D034281:Dynamins; C439628:shi protein, Drosophila