title: Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast.
abstract: Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2(+) gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity.
authors.affiliation: Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kita
authors.affiliation: Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Higa
authors.affiliation: Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan; Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Doi
authors.affiliation: Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Satoh
authors.affiliation: Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan. Electronic address: sugiurar@phar.kindai.ac.jp.
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugiura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D002473:Cell Wall / Q000378:metabolism / Q000648:ultrastructure; D003001:Cloning, Molecular; D048749:Cytokinesis / Q000187:drug effects / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D012568:Schizosaccharomyces / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C535064:IMP2 protein, S pombe; D007166:Immunosuppressive Agents; C110097:Pstpip1 protein, mouse; D029702:Schizosaccharomyces pombe Proteins; D016559:Tacrolimus
keywords: Calcineurin; Cytokinesis; Fission yeast; Membrane trafficking; Proline-serine-threonine phosphatase interacting protein