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Cilium Length and Intraflagellar Transport Regulation by Kinases PKG-1 and GCK-2 in Caenorhabditis elegans Sensory Neurons.
Muthaiyan Shanmugam, Muniesh; Bhan, Prerana; Huang, Hsin-Yi; Hsieh, Jung; Hua, Tzu-En; Wu, Gong-Her; Punjabi, Helly; Lee Aplícano, Víctor Daniel; Chen, Chih-Wei; Wagner, Oliver Ingvar.
Afiliação
  • Muthaiyan Shanmugam M; National Tsing Hua University, Institute of Molecular and Cellular Biology, Department of Life Science, Hsinchu, Taiwan, Republic of China.
  • Bhan P; National Tsing Hua University, Institute of Molecular and Cellular Biology, Department of Life Science, Hsinchu, Taiwan, Republic of China.
  • Huang HY; National Tsing Hua University, Institute of Molecular and Cellular Biology, Department of Life Science, Hsinchu, Taiwan, Republic of China.
  • Hsieh J; National Tsing Hua University, Institute of Molecular and Cellular Biology, Department of Life Science, Hsinchu, Taiwan, Republic of China.
  • Hua TE; Electron Microscopy Core Facility, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
  • Wu GH; National Tsing Hua University, Institute of Molecular and Cellular Biology, Department of Life Science, Hsinchu, Taiwan, Republic of China.
  • Punjabi H; National Tsing Hua University, Institute of Molecular and Cellular Biology, Department of Life Science, Hsinchu, Taiwan, Republic of China.
  • Lee Aplícano VD; National Tsing Hua University, Institute of Molecular and Cellular Biology, Department of Life Science, Hsinchu, Taiwan, Republic of China.
  • Chen CW; National Tsing Hua University, Institute of Molecular and Cellular Biology, Department of Life Science, Hsinchu, Taiwan, Republic of China.
  • Wagner OI; National Tsing Hua University, Institute of Molecular and Cellular Biology, Department of Life Science, Hsinchu, Taiwan, Republic of China owagner@life.nthu.edu.tw.
Mol Cell Biol ; 38(7)2018 04 01.
Article em En | MEDLINE | ID: mdl-29378827
ABSTRACT
To understand how ciliopathies such as polycystic kidney disease or Bardet-Biedl syndrome develop, we need to understand the basic molecular mechanisms underlying cilium development. Cilium growth depends on the presence of functional intraflagellar transport (IFT) machinery, and we hypothesized that various kinases and phosphatases might be involved in this regulatory process. A candidate screen revealed two kinases, PKG-1 (a cGMP-dependent protein kinase) and GCK-2 (a mitogen-activated protein kinase kinase kinase kinase 3 [MAP4K3] kinase involved in mTOR signaling), significantly affecting dye filling, chemotaxis, cilium morphology, and IFT component distribution. PKG-1 and GCK-2 show similar expression patterns in Caenorhabditis elegans cilia and colocalize with investigated IFT machinery components. In pkg-1 mutants, a high level of accumulation of kinesin-2 OSM-3 in distal segments was observed in conjunction with an overall reduction of anterograde and retrograde IFT particle A transport, likely as a function of reduced tubulin acetylation. In contrast, in gck-2 mutants, both kinesin-2 motility and IFT particle A motility were significantly elevated in the middle segments, in conjunction with increased tubulin acetylation, possibly the cause of longer cilium growth. Observed effects in mutants can be also seen in manipulating upstream and downstream effectors of the respective cGMP and mTOR pathways. Importantly, transmission electron microscopy (TEM) analysis revealed no structural changes in cilia of pkg-1 and gck-2 mutants.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Receptoras Sensoriais / Cílios / Proteínas Serina-Treonina Quinases / Proteínas Quinases Dependentes de GMP Cíclico / Proteínas de Caenorhabditis elegans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Receptoras Sensoriais / Cílios / Proteínas Serina-Treonina Quinases / Proteínas Quinases Dependentes de GMP Cíclico / Proteínas de Caenorhabditis elegans Idioma: En Ano de publicação: 2018 Tipo de documento: Article