pH-dependent cargo sorting from the Golgi.
The vacuolar proton-translocating ATPase (V-ATPase) plays a major role in organelle acidification and works together with other ion transporters to maintain pH homeostasis in eukaryotic cells. We analyzed a requirement for V-ATPase activity in protein trafficking in the yeast secretory pathway. Deficiency of V-ATPase activity caused by subunit deletion or glucose deprivation results in missorting of newly synthesized plasma membrane proteins Pma1 and Can1 directly from the Golgi to the vacuole. Vacuolar mislocalization of Pma1 is dependent on Gga adaptors although no Pma1 ubiquitination was detected. Proper cell surface targeting of Pma1 was rescued in V-ATPase-deficient cells by increasing the pH of the medium, suggesting that missorting is the result of aberrant cytosolic pH. In addition to mislocalization of the plasma membrane proteins, Golgi membrane proteins Kex2 and Vrg4 are also missorted to the vacuole upon loss of V-ATPase activity. Because the missorted cargos have distinct trafficking routes, we suggest a pH dependence for multiple cargo sorting events at the Golgi.
Department of Molecular, Cellular & Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Chunjuan
C
Huang
Amy
A
Chang
D026923:Amino Acid Transport Systems, Basic / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*
D026923:Amino Acid Transport Systems, Basic; C502212:CAN1 protein, S cerevisiae; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; C099493:VRG4 protein, S cerevisiae; D043484:Proprotein Convertases; C058751:KEX2 protein, S cerevisiae; C092477:PMA1 protein, S cerevisiae; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases; D005947:Glucose
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