RRC ID 884
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
Abstract 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.
Volume 15(6)
Pages 2920-31
Published 2004-6-1
DOI 10.1091/mbc.e03-09-0659
PII E03-09-0659
PMID 15047861
PMC PMC420114
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
IF 3.791
Times Cited 64
Yeast HM123