High impact information on GCS1

• Our results demonstrate that the Gcs1 + Age2 ArfGAP pair provides overlapping function for transport from the TGN, and also indicate that multiple activities at the TGN can be maintained with the aid of a single ArfGAP [1].
• Further, we demonstrate novel direct interactions of coatomer subunits with regulatory proteins: beta'- and gamma-COP interact with the ARF-GTP-activating protein (GAP) Glo3p, but not Gcs1p, and beta- and epsilon-COP interact with ARF-GTP [2].
• The cloning and molecular characterization of the GCS1 gene from the budding yeast Saccharomyces cerevisiae show that stationary phase is in fact a unique developmental state, with requirements to resume cell proliferation that can be distinct from those for maintenance of proliferation [3].
• A point mutation within the finger motif produces a phenotype that mimics that of deletion of the GCS1 gene, showing that the finger motif is essential for full Gcs1p activity [3].
• The budding yeast Saccharomyces cerevisiae contains a family of Arf (ADP-ribosylation factor) GTPase activating protein (GAP) proteins with the Gcs1 + Age2 ArfGAP pair providing essential overlapping function for the movement of transport vesicles from the trans-Golgi network [4].

Biological context of GCS1

• The GCS1 gene of the budding yeast Saccharomyces cerevisiae mediate the resumption of cell proliferation from the starved, stationary-phase state [5].
• GCS1 was originally identified as a gene conditionally required for the reentry of cells into the cell cycle after stationary phase growth [6].
• An impairment in endocytosis was found for gcs1 delta mutant cells, which was alleviated by an increased YCK2 gene dosage [5].
• For gcs1 delta suppression, both a protein kinase domain and a C-terminal prenylation motif were shown to be necessary [5].
• Herein, we searched for Arf regulator genes whose mutations were synthetically lethal with cdc50Delta, and identified the Arf GAP gene GCS1 [7].

Anatomical context of GCS1

• Synthetic lethality was observed between null alleles of GCS1 and SLA2, the gene encoding a protein involved in stabilization of the actin cytoskeleton [6].
• Furthermore, Gcs1 function is needed for the efficient secretion of invertase, as expected for a component of vesicle transport [8].
• The Gcs1 and Age2 ArfGAP proteins provide overlapping essential function for transport from the yeast trans-Golgi network [1].
• Genetic and in vitro approaches reveal that Glo3 and Gcs1 have an overlapping essential function at the endoplasmic reticulum (ER)-Golgi stage of vesicular transport [9].
• In gcs1 mutant cells, the fraction of Arl1p in cytosol relative to trans-Golgi was less than it was in wild-type cells [10].

Associations of GCS1 with chemical compounds

• A novel GCS1 disruption strain (gcs1Delta) exhibited morphological defects, as well as mislocalization of cortical actin patches. gcs1Delta was hypersensitive to the actin monomer-sequestering drug, latrunculin-B [6].
• Here, we have shown that similar to centaurin alpha, recombinant Gcs1p bound phosphoinositide-based affinity resins with high affinity and specificity [6].
• Gcs1p was previously characterized as a guanosine triphosphatase-activating protein for the small guanosine triphosphatase Arf1, and gcs1 mutants displayed vesicle-trafficking defects [6].
• Interestingly, cells deleted for GCS1 have reduced levels of Spo14p-generated PA [11].
• Identification of centaurin-alpha1 as a potential in vivo phosphatidylinositol 3,4,5-trisphosphate-binding protein that is functionally homologous to the yeast ADP-ribosylation factor (ARF) GTPase-activating protein, Gcs1 [12].

Physical interactions of GCS1

• These data provide in vivo and in vitro evidence that Gcs1p interacts directly with the actin cytoskeleton in S. cerevisiae [6].

Regulatory relationships of GCS1

• Taken together, these results indicate that GCS1 is essential for sporulation and suggest that GCS1 positively regulates SPO14 [11].

Other interactions of GCS1

• Prenylated isoforms of yeast casein kinase I, including the novel Yck3p, suppress the gcs1 blockage of cell proliferation from stationary phase [5].
• In addition, synthetic growth defects were observed between null alleles of GCS1 and SAC6, the gene encoding the yeast fimbrin homologue [6].
• Saccharomyces cerevisiae Gcs1 is an ADP-ribosylation factor GTPase-activating protein [8].
• Only gcs1delta mutants display a sporulation defect similar to that of spo14 mutants: cells deleted for GCS1 initiate the sporulation program but are defective in synthesis of the prospore membrane [11].
• Role for Gcs1p in regulation of Arl1p at trans-Golgi compartments [10].

References