Loss of Apm1, the μ1 subunit of the clathrin-associated adaptor-protein-1 complex, causes distinct phenotypes and synthetic lethality with calcineurin deletion in fission yeast

Ayako Kita, Reiko Sugiura, Hiromi Shoji, Yi He, Lu Deng, Yabin Lu, Susie O. Sio, Kaoru Takegawa, Motoyoshi Sakaue, Hisato Shuntoh, Takayoshi Kuno

Research output: Contribution to journalArticle

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Abstract

Calcineurin is a highly conserved regulator of Ca2+ 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 μ1A subunit of the clathrin-associated adaptor protein-1 (AP-1) complex. The cis1-1/apm1-1 mutant as well as the apm1-deleted (Δapm1) cells showed distinct phenotypes: temperature sensitivity; tacrolimus (FK506) sensitivity; and pleiotropic defects in cytokinesis, cell integrity, and vacuole fusion. Electron micrographs revealed that Δapm1 cells showed large vesicular structures associated with Golgi stacks and accumulated post-Golgi secretory vesicles. Δapm1 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.

Original languageEnglish
Pages (from-to)2920-2931
Number of pages12
JournalMolecular biology of the cell
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 1 2004
Externally publishedYes

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Vesicular Transport Adaptor Proteins
Schizosaccharomyces
Calcineurin
Cytokinesis
Endosomes
Tacrolimus
Phenotype
Vacuoles
Spindle Pole Bodies
SNARE Proteins
Body Regions
Mutation
Temperature
Cell Fusion
Secretory Pathway
Secretory Vesicles
Acid Phosphatase
Eukaryota
Homeostasis
Alleles

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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Loss of Apm1, the μ1 subunit of the clathrin-associated adaptor-protein-1 complex, causes distinct phenotypes and synthetic lethality with calcineurin deletion in fission yeast. / Kita, Ayako; Sugiura, Reiko; Shoji, Hiromi; He, Yi; Deng, Lu; Lu, Yabin; Sio, Susie O.; Takegawa, Kaoru; Sakaue, Motoyoshi; Shuntoh, Hisato; Kuno, Takayoshi.

In: Molecular biology of the cell, Vol. 15, No. 6, 01.06.2004, p. 2920-2931.

Research output: Contribution to journalArticle

Kita, Ayako ; Sugiura, Reiko ; Shoji, Hiromi ; He, Yi ; Deng, Lu ; Lu, Yabin ; Sio, Susie O. ; Takegawa, Kaoru ; Sakaue, Motoyoshi ; Shuntoh, Hisato ; Kuno, Takayoshi. / Loss of Apm1, the μ1 subunit of the clathrin-associated adaptor-protein-1 complex, causes distinct phenotypes and synthetic lethality with calcineurin deletion in fission yeast. In: Molecular biology of the cell. 2004 ; Vol. 15, No. 6. pp. 2920-2931.
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AU - Sugiura, Reiko

AU - Shoji, Hiromi

AU - He, Yi

AU - Deng, Lu

AU - Lu, Yabin

AU - Sio, Susie O.

AU - Takegawa, Kaoru

AU - Sakaue, Motoyoshi

AU - Shuntoh, Hisato

AU - Kuno, Takayoshi

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AB - Calcineurin is a highly conserved regulator of Ca2+ 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 μ1A subunit of the clathrin-associated adaptor protein-1 (AP-1) complex. The cis1-1/apm1-1 mutant as well as the apm1-deleted (Δapm1) cells showed distinct phenotypes: temperature sensitivity; tacrolimus (FK506) sensitivity; and pleiotropic defects in cytokinesis, cell integrity, and vacuole fusion. Electron micrographs revealed that Δapm1 cells showed large vesicular structures associated with Golgi stacks and accumulated post-Golgi secretory vesicles. Δapm1 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.

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