title: Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast.
abstract: The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells.
authors: Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501, Japan.
authors: Yuta
authors: Y
authors: Tsukamoto
authors: Department of Biological Sciences, Faculty of Science, Nara Women's University, Kitauoyanishi-machi, Nara 630-8506, Japan.
authors: Satoshi
authors: S
authors: Kagiwada
authors: Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501, Japan.
authors: Sayuri
authors: S
authors: Shimazu
authors: Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors: Kaoru
authors: K
authors: Takegawa
authors: Department of Biological Sciences, Faculty of Science, Nara Women's University, Kitauoyanishi-machi, Nara 630-8506, Japan.
authors: Tetsuko
authors: T
authors: Noguchi
authors: Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501, Japan; Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501, Japan. Electronic address: miya@kobe-u.ac.jp.
authors: Masaaki
authors: M
authors: Miyamoto
mesh_terms: D002268:Carboxypeptidases / Q000378:metabolism; D017353:Gene Deletion; D020662:Guanine Nucleotide Exchange Factors; D009154:Mutation; D021381:Protein Transport; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D029702:Schizosaccharomyces pombe Proteins; C000597860:Vps901 protein, S pombe; C000597861:Vps902 protein, S pombe; D002268:Carboxypeptidases; C022326:penicillocarboxypeptidase-S; D020696:rab5 GTP-Binding Proteins
keywords: Fission yeast; Rab5; VPS9 protein