Activity of specific lipid-regulated ADP ribosylation factor-GTPase-activating proteins is required for Sec14p-dependent Golgi secretory function in yeast.
Yeast phosphatidylinositol transfer protein (Sec14p) coordinates lipid metabolism with protein-trafficking events. This essential Sec14p requirement for Golgi function is bypassed by mutations in any one of seven genes that control phosphatidylcholine or phosphoinositide metabolism. In addition to these "bypass Sec14p" mutations, Sec14p-independent Golgi function requires phospholipase D activity. The identities of lipids that mediate Sec14p-dependent Golgi function, and the identity of the proteins that respond to Sec14p-mediated regulation of lipid metabolism, remain elusive. We now report genetic evidence to suggest that two ADP ribosylation factor-GTPase-activating proteins (ARFGAPs), Gcs1p and Age2p, may represent these lipid-responsive elements, and that Gcs1p/Age2p act downstream of Sec14p and phospholipase D in both Sec14p-dependent and Sec14p-independent pathways for yeast Golgi function. In support, biochemical data indicate that Gcs1p and Age2p ARFGAP activities are both modulated by lipids implicated in regulation of Sec14p pathway function. These results suggest ARFGAPs are stimulatory factors required for regulation of Golgi function by the Sec14p pathway, and that Sec14p-mediated regulation of lipid metabolism interfaces with the activity of proteins involved in control of the ARF cycle.
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Lora L
LL
Yanagisawa
Jennifer
J
Marchena
Zhigang
Z
Xie
Xinmin
X
Li
Pak P
PP
Poon
Richard A
RA
Singer
Gerald C
GC
Johnston
Paul A
PA
Randazzo
Vytas A
VA
Bankaitis
D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001692:Biological Transport / Q000502:physiology; D001798:Blood Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
C444920:AGE2 protein, S cerevisiae; D001798:Blood Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C089147:GCS1 protein, S cerevisiae; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D010750:Phosphoproteins; D011994:Recombinant Proteins; C118289:SEC24 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C039077:platelet protein P47; D010739:Phospholipase D; D020727:ADP-Ribosylation Factors