Reference - Detail
|Author||Kita A, Sugiura R, Shoji H, He Y, Deng L, Lu Y, Sio SO, Takegawa K, Sakaue M, Shuntoh H, Kuno T.|
|Title||Loss of Apm1, the micro1 subunit of the clathrin-associated adaptor-protein-1 complex, causes distinct phenotypes and synthetic lethality with calcineurin deletion in fission yeast.|
|Journal||Mol. Biol. Cell|
Calcineurin is a highly conserved regulator of Ca(2+) signaling in eukaryotes. In fission yeast, calcineurin is not essential for viability but is required for cytokinesis and Cl(-) homeostasis. In a genetic screen for mutations that are synthetically lethal with calcineurin deletion, we isolated a mutant, cis1-1/apm1-1, an allele of the apm1(+) gene that encodes a homolog of the mammalian micro1A subunit of the clathrin-associated adaptor protein-1 (AP-1) complex. The cis1-1/apm1-1 mutant as well as the apm1-deleted (Deltaapm1) cells showed distinct phenotypes: temperature sensitivity; tacrolimus (FK506) sensitivity; and pleiotropic defects in cytokinesis, cell integrity, and vacuole fusion. Electron micrographs revealed that Deltaapm1 cells showed large vesicular structures associated with Golgi stacks and accumulated post-Golgi secretory vesicles. Deltaapm1 cells also showed the massive accumulation of the exocytic v-SNARE Syb1 in the Golgi/endosomes and a reduced secretion of acid phosphatase. These phenotypes observed in apm1 mutations were accentuated upon temperature up-shift and FK506 treatment. Notably, Apm1-GFP localized to the Golgi/endosomes, the spindle pole bodies, and the medial region. These findings suggest a role for Apm1 associated with the Golgi/endosome function, thereby affecting various cellular processes, including secretion, cytokinesis, vacuole fusion, and cell integrity and also suggest that calcineurin is involved in these events.
|MeSH||Acid Phosphatase / metabolism Adaptor Protein Complex 1 / chemistry Adaptor Protein Complex 1 / genetics Adaptor Protein Complex 1 / metabolism* Adaptor Protein Complex mu Subunits / deficiency* Adaptor Protein Complex mu Subunits / genetics Adaptor Protein Complex mu Subunits / metabolism Amino Acid Sequence Calcineurin / deficiency* Calcineurin / genetics Calcineurin / metabolism Cell Wall / physiology Cytokinesis Endocytosis Endosomes / metabolism Gene Deletion* Genes, Fungal / genetics Genes, Lethal / genetics* Golgi Apparatus / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Molecular Sequence Data Osmotic Pressure Phenotype Promoter Regions, Genetic / genetics Protein Subunits / deficiency Protein Subunits / genetics Protein Subunits / metabolism R-SNARE Proteins Saccharomyces cerevisiae Proteins / genetics Saccharomyces cerevisiae Proteins / metabolism Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism* Schizosaccharomyces / ultrastructure Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism Secretory Vesicles / metabolism Spindle Apparatus / metabolism rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism|
|WOS Category||CELL BIOLOGY|