A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway.
Genetic screens in the yeast Saccharomyces cerevisiae have identified many proteins involved in the secretory pathway, most of which have orthologues in higher eukaryotes. To investigate whether there are additional proteins that are required for secretion in metazoans but are absent from yeast, we used genome-wide RNA interference (RNAi) to look for genes required for secretion of recombinant luciferase from Drosophila S2 cells. This identified two novel components of the secretory pathway that are conserved from humans to plants. Gryzun is distantly related to, but distinct from, the Trs130 subunit of the TRAPP complex but is absent from S. cerevisiae. RNAi of human Gryzun (C4orf41) blocks Golgi exit. Kish is a small membrane protein with a previously uncharacterised orthologue in yeast. The screen also identified Drosophila orthologues of almost 60% of the yeast genes essential for secretion. Given this coverage, the small number of novel components suggests that contrary to previous indications the number of essential core components of the secretory pathway is not much greater in metazoans than in yeasts.
Wendler
Franz
F
MRC National Institute for Medical Research, London, UK.
Gillingham
Alison K
AK
Sinka
Rita
R
Rosa-Ferreira
Cláudia
C
Gordon
David E
DE
Franch-Marro
Xavier
X
Peden
Andrew A
AA
Vincent
Jean-Paul
JP
Munro
Sean
S
D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism; D017344:Genes, Insect; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D034622:RNA Interference; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D055571:Secretory Pathway
D029721:Drosophila Proteins