Energy metabolism regulates clathrin adaptors at the trans-Golgi network and endosomes.
Glucose is a master regulator of cell behavior in the yeast Saccharomyces cerevisiae. It acts as both a metabolic substrate and a potent regulator of intracellular signaling cascades. Glucose starvation induces the transient delocalization and then partial relocalization of clathrin adaptors at the trans-Golgi network and endosomes. Although these localization responses are known to depend on the protein kinase A (PKA) signaling pathway, the molecular mechanism of this regulation is unknown. Here we demonstrate that PKA and the AMP-regulated kinase regulate adaptor localization through changes in energy metabolism. We show that genetic and chemical manipulation of intracellular ATP levels cause corresponding changes in adaptor localization. In permeabilized cells, exogenous ATP is sufficient to induce adaptor localization. Furthermore, we reveal distinct energy-dependent steps in adaptor localization: a step that requires the ADP-ribosylation factor ARF, an ATP-dependent step that requires the phosphatidyl-inositol-4 kinase Pik1, and third ATP-dependent step for which we provide evidence but for which the mechanism is unknown. We propose that these energy-dependent mechanisms precisely synchronize membrane traffic with overall proliferation rates and contribute a crucial aspect of energy conservation during acute glucose starvation.
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Quyen L
QL
Aoh
Chao-wei
CW
Hung
Mara C
MC
Duncan
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D033961:Adaptor Protein Complex 1 / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D021601:trans-Golgi Network / Q000378:metabolism*
D033961:Adaptor Protein Complex 1; D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; C071570:SNF1-related protein kinases; D019870:1-Phosphatidylinositol 4-Kinase; C441760:PIK1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases; D020727:ADP-Ribosylation Factors; D005947:Glucose