Yeast Ysl2p, homologous to Sec7 domain guanine nucleotide exchange factors, functions in endocytosis and maintenance of vacuole integrity and interacts with the Arf-Like small GTPase Arl1p

Mol Cell Biol. 2002 Jul;22(13):4914-28. doi: 10.1128/MCB.22.13.4914-4928.2002.


We previously described the isolation of ysl2-1 due to its genetic interaction with Delta ypt51/vps21, a mutant with a deletion of the coding sequence for the yeast Rab5 homolog, which regulates endocytic traffic between early and late endosomes. Here we report that Ysl2p is a novel 186.8-kDa peripheral membrane protein homologous to members of the Sec7 family. We provide multiple genetic and biochemical evidence for an interaction between Ysl12p and the Arf-like protein Arl1p, consistent with a potential function as an Arf guanine nucleotide exchange factor (GEF). The temperature-sensitive alleles ysl2-307 and ysl2-316 are specifically defective in ligand-induced degradation of Ste2p and alpha-factor and exhibit vacuole fragmentation directly upon a shift to 37 degrees C. In living cells, green fluorescent protein (GFP)-Ysl2p colocalizes with endocytic elements that accumulate FM4-64. The GFP-Ysl2p staining is sensitive to a mutation in VPS27 resulting in the formation of an aberrant class E compartment, but it is not affected by a sec7 mutation. Consistent with the idea that Ysl2p and Arl1p have closely related functions, Delta arl1 cells are defective in endocytic transport and in vacuolar protein sorting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors*
  • Amino Acid Sequence
  • Base Sequence
  • Carboxypeptidases / metabolism
  • Cathepsin A
  • Endocytosis*
  • Endosomes / metabolism
  • Fluorescent Dyes / chemistry
  • Fungal Proteins / metabolism
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Glycoside Hydrolases / metabolism
  • Green Fluorescent Proteins
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Intracellular Membranes / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Organic Anion Transporters, Sodium-Dependent / genetics
  • Organic Anion Transporters, Sodium-Dependent / metabolism*
  • Pyridinium Compounds / chemistry
  • Quaternary Ammonium Compounds / chemistry
  • Sequence Analysis
  • Sequence Homology, Amino Acid
  • Sodium-Coupled Vitamin C Transporters
  • Symporters*
  • Temperature
  • Vacuoles / metabolism
  • Vacuoles / ultrastructure*
  • beta-Fructofuranosidase


  • FM 4-64
  • Fluorescent Dyes
  • Fungal Proteins
  • Guanine Nucleotide Exchange Factors
  • Luminescent Proteins
  • Membrane Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Sec7 guanine nucleotide exchange factors
  • Sodium-Coupled Vitamin C Transporters
  • Symporters
  • Green Fluorescent Proteins
  • Glycoside Hydrolases
  • beta-Fructofuranosidase
  • Carboxypeptidases
  • Cathepsin A
  • ADP-ribosylation factor related proteins
  • GTP Phosphohydrolases
  • ADP-Ribosylation Factors