title: Tpd3-Pph21 phosphatase plays a direct role in Sep7 dephosphorylation in Candida albicans.
abstract: Septins are a component of the cytoskeleton and play important roles in diverse cellular processes including cell cycle control, cytokinesis and polarized growth. In fungi, septin organization, dynamics and function are regulated by phosphorylation, and several kinases responsible for the phosphorylation of several septins have been identified. However, little is known about the phosphatases that dephosphorylate septins. Here, we report the characterization of Tpd3, a structural subunit of the PP2A family of phosphatases, in the pathogenic fungus Candida albicans. We found that tpd3Δ/Δ cells are defective in hyphal growth and grow as pseudohyphae under yeast growth conditions with aberrant septin organization. Western blotting detected hyperphosphorylation of the septin Sep7 in cells lacking Tpd3. Tpd3 and Sep7 colocalize at the bud neck and can coimmunoprecipitate. Furthermore, we discovered similar defects in cells lacking Pph21, a catalytic subunit of the PP2A family, and its physical association with Tpd3. Importantly, purified Tpd3-Pph21 complexes can dephosphorylate Sep7 in vitro. Together, our findings strongly support the idea that the Tpd3-Pph21 complex dephosphorylates Sep7 and regulates morphogenesis and cytokinesis. The tpd3Δ/Δ mutant is greatly reduced in virulence in mice, providing a potential antifungal target.
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Qizheng
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Han
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Guangyin
authors.initials: G
authors.lastname: Yao
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Zeng
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Sang
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D025301:Hyphae / Q000254:growth & development; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D058112:Septins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D054648:Protein Phosphatase 2; D058112:Septins