ATP uptake in the Golgi and extracellular release require Mcd4 protein and the vacuolar H+-ATPase.
Extracellular nucleotides signal via a large group of purinergic receptors. Although much is known about these receptors, the mechanism of nucleotide transport out of the cytoplasm is unknown. We developed a functional screen for ATP release to the extracellular space and identified Mcd4p, a 919-amino acid membrane protein with 14 putative transmembrane domains, as a participant in glucose-dependent ATP release from Saccharomyces cerevisiae. This release occurred through the vesicular trafficking pathway initiated by ATP uptake into the Golgi compartment. Both the compartmental uptake and the extracellular release of ATP were regulated by the activity of the vacuolar H+-ATPase. It is likely that the Mcd4p pathway is generally involved in non-mitochondrial ATP movement across membranes, it is essential for Golgi and endoplasmic reticulum function, and its occurrence led to the appearance of P2 purinergic receptors.
Zhong
Xiaotian
X
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Malhotra
Rajeev
R
Guidotti
Guido
G
D000225:Adenine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000493:pharmacokinetics*; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
C118052:MCD4 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D005947:Glucose; D000225:Adenine; D005690:Galactose