3 years ago

Cilia length and intraflagellar transport regulation by kinases PKG-1 and GCK-2 in C. elegans sensory neurons.

Jung Hsieh, Prerana Bhan, Chih-Wei Chen, Helly Punjabi, Muniesh Muthaiyan Shanmugam, Gong-Her Wu, Víctor Daniel Lee Aplícano, Tzu-En Hua, Hsin-Yi Huang, Oliver Ingvar Wagner
To understand how ciliopathies such as polycystic kidney disease or Bardet-Biedl syndrome develop, we need to understand the basic molecular mechanisms underlying cilia development. Cilia growth depends on a 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 MAP4K3 kinase involved in mTOR signaling) significantly affecting dye filling, chemotaxis, cilia morphology, and IFT component distribution. Both, PKG-1 and GCK-2 follow similar expression pattern in C. elegans cilia, and colocalize with investigated IFT machinery components. In pkg-1 mutants, severe 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 and IFT particle A motility was significantly elevated in the middle segments, in conjunction with increased tubulin acetylation, possibly the cause of longer cilia growth. Observed effects in mutants can be also seen when manipulating upstream and downstream effectors of respective cGMP and mTOR pathways. Importantly, TEM analysis revealed no structural changes in cilia of pkg-1 and gck-2 mutants.

Publisher URL: http://doi.org/10.1128/MCB.00612-17

DOI: 10.1128/MCB.00612-17

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