Receptor internalization in yeast requires the Tor2-Rho1 signaling pathway.
Efficient internalization of proteins from the cell surface is essential for regulating cell growth and differentiation. In a screen for yeast mutants defective in ligand-stimulated internalization of the alpha-factor receptor, we identified a mutant allele of TOR2, tor2G2128R. Tor proteins are known to function in translation initiation and nutrient sensing and are required for cell cycle progression through G1. Yeast Tor2 has an additional role in regulating the integrity of the cell wall by activating the Rho1 guanine nucleotide exchange factor Rom2. The endocytic defect in tor2G2128R cells is due to disruption of this Tor2 unique function. Other proteins important for cell integrity, Rom2 and the cell integrity sensor Wsc1, are also required for efficient endocytosis. A rho1 mutant specifically defective in activation of the glucan synthase Fks1/2 does not internalize alpha-factor efficiently, and fks1Delta cells exhibit a similar phenotype. Removal of the cell wall does not inhibit internalization, suggesting that the function of Rho1 and Fks1 in endocytosis is not through cell wall synthesis or structural integrity. These findings reveal a novel function for the Tor2-Rho1 pathway in controlling endocytosis in yeast, a function that is mediated in part through the plasma membrane protein Fks1.
Department of Biochemistry, Molecular Biology and Cell Biology Northwestern University, Evanston, Illinois 60208, USA.
Amy K A
AK
deHart
Joshua D
JD
Schnell
Damian A
DA
Allen
Ju-Yun
JY
Tsai
Linda
L
Hicke
D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism* / Q000502:physiology; D002473:Cell Wall / Q000378:metabolism / Q000502:physiology; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D016193:G1 Phase; D020662:Guanine Nucleotide Exchange Factors; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism* / Q000502:physiology; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D029701:Saccharomyces cerevisiae Proteins; D020741:rho GTP-Binding Proteins; C490929:ROM2 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae; C051302:RHO1 protein, S cerevisiae