Primary cilia are ubiquitous sensory organelles that mediate diverse signaling pathways. Cilia position on the cell surface is determined by the location of the basal body (BB) that templates the cilium. The mechanisms that regulate BB positioning in the context of ciliogenesis are largely unknown. Here we show that the conserved signaling and scaffolding protein Girdin localizes to the proximal regions of centrioles and regulates BB positioning and ciliogenesis in Caenorhabditis elegans sensory neurons and human RPE-1 cells. Girdin depletion alters localization of the intercentriolar linker and ciliary rootlet component rootletin, and rootletin knockdown in RPE-1 cells mimics Girdin-dependent phenotypes. C. elegans Girdin also regulates localization of the apical junction component AJM-1, suggesting that in nematodes Girdin may position BBs via rootletin- and AJM-1-dependent anchoring to the cytoskeleton and plasma membrane, respectively. Together, our results describe a conserved role for Girdin in BB positioning and ciliogenesis.
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http://dx.doi.org/10.1016/j.devcel.2016.07.013 | DOI Listing |
iScience
December 2024
Department of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, Boler-Parseghian Center for Rare and Neglected Diseases, Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, IN 46556, USA.
Cilia are hair-like organelles with vital physiological roles, and ciliogenesis defects underlie a range of severe congenital malformations and human diseases. Here, we report that is essential for cilia development across multiple embryonic tissues including the ear, neuromasts and Kupffer's vesicle (KV), which establishes left/right axial pattern. deficient embryos manifest altered fluid homeostasis and kidney defects including decreased multiciliated cells (MCCs), determining that is essential to properly establish several renal lineages.
View Article and Find Full Text PDFDevelopment
November 2024
Department of Genetics, University of Georgia, Athens, GA 30602, USA.
The establishment of CRISPR/Cas9 gene editing in Anolis sagrei has positioned this species as a powerful model for studies of reptilian gene function. To enhance this model, we developed an immortalized lizard fibroblast cell line (ASEC-1) for the exploration of reptilian gene function in cellular processes. We demonstrate the use of this cell line by scrutinizing the role of primary cilia in lizard Hedgehog (Hh) signaling.
View Article and Find Full Text PDFCalibrated transcriptional outputs in cellular signaling require fine regulation of transcription factor activity. In vertebrate Hedgehog (Hh) signaling, the precise output of the final effectors, the GLI (Glioma-associated-oncogene) transcription factors, depends on the primary cilium. In particular, the formation of the activator form of GLI upon pathway initiation requires its concentration at the distal cilium tip.
View Article and Find Full Text PDFCancer Res
December 2024
Biobank of Tumors from Plateau of Gansu Province, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, People's Republic of China.
Primary cilia detect and transmit environmental signals into cells. Primary cilia are absent in a subset of ductal carcinomas characterized by distinctive biological activities, and recovery of cilia with normal functionality has been shown to have therapeutic potential in some cancer types. Therefore, elucidation of the underlying mechanism and clinical significance of ciliary loss in ductal carcinomas could help develop effective treatment strategies.
View Article and Find Full Text PDFDev Dyn
December 2024
Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Primary cilia are antenna-like sensory organelles that are evolutionarily conserved in nearly all modern eukaryotes, from the single-celled green alga, Chlamydomonas reinhardtii, to vertebrates and mammals. Cilia are microtubule-based cellular projections that have adapted to perform a broad range of species-specific functions, from cell motility to detection of light and the transduction of extracellular mechanical and chemical signals. These functions render cilia essential for organismal development and survival.
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