scholarly journals Hedgehog signaling and the primary cilium: implications for spatial and temporal constraints on signaling

Development ◽  
2021 ◽  
Vol 148 (9) ◽  
Author(s):  
Emily K. Ho ◽  
Tim Stearns
Keyword(s):  
Signal Transduction ◽  
Primary Cilium ◽  
Hedgehog Signaling ◽  
Cell Types ◽  
Spatial Constraints ◽  
Vertebrate Cell ◽  
Temporal And Spatial ◽  
Hedgehog Signal Transduction ◽  
Hedgehog Signal

ABSTRACT The mechanisms of vertebrate Hedgehog signaling are linked to the biology of the primary cilium, an antenna-like organelle that projects from the surface of most vertebrate cell types. Although the advantages of restricting signal transduction to cilia are often noted, the constraints imposed are less frequently considered, and yet they are central to how Hedgehog signaling operates in developing tissues. In this Review, we synthesize current understanding of Hedgehog signal transduction, ligand secretion and transport, and cilia dynamics to explore the temporal and spatial constraints imposed by the primary cilium on Hedgehog signaling in vivo.

scholarly journals DYRK2 is a ciliary kinase involved in vertebrate Hedgehog signal transduction

2020 ◽  
Author(s):  
Nicholas Morante ◽  
Monika Abedin Sigg ◽  
Luke Strauskulage ◽  
David R. Raleigh ◽  
Jeremy F. Reiter
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Skeletal Development ◽  
Skeletal Defects ◽  
Gli Transcription Factors ◽  
Hedgehog Signal Transduction ◽  
Hedgehog Signal

ABSTRACTPrimary cilia are organelles specialized for signaling. We previously defined the proteomes of sea urchin and sea anemone cilia to identify ciliary proteins that predate the origin of bilateria. This evolutionary perspective on cilia identified DYRK2, a kinase not been previously implicated in ciliary biology. We found that DYRK2 localizes to cilia and that loss of DYRK2 disrupts ciliary morphology. We also found that DYRK2 participates in ciliary Hh signal transduction, communicating between SMO and GLI transcription factors. Mutation of mouse Dyrk2 resulted in skeletal defects reminiscent of those caused by loss of Indian hedgehog (Ihh). Like Dyrk2 mutations, pharmacological inhibition of DYRK2 dysregulates ciliary length control and attenuates Hedgehog signaling. Thus, DYRK2 is required for ciliary morphology, for Hedgehog signaling in vitro, and for skeletal development. We propose that DYRK2 is part of the mechanism that transduces SMO to activate GLI transcription factors within cilia.

Regulation of primary cilia formation by the ubiquitin–proteasome system

2016 ◽  
Vol 44 (5) ◽  
pp. 1265-1271 ◽  
Author(s):  
Robert F. Shearer ◽  
Darren N. Saunders
Keyword(s):  
Signal Transduction ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Cell Types ◽  
Ubiquitin Proteasome System ◽  
Signal Transduction Pathways ◽  
Vertebrate Cell ◽  
Cilia Formation ◽  
Ubiquitin Proteasome ◽  
Novel Therapeutic

Primary cilia form at the surface of most vertebrate cell types, where they are essential signalling antennae for signal transduction pathways important for development and cancer, including Hedgehog. The importance of primary cilia in development is clearly demonstrated by numerous disorders (known as ciliopathies) associated with disrupted cilia formation (ciliogenesis). Recent advances describing functional regulators of the primary cilium highlight an emerging role for the ubiquitin–proteasome system (UPS) as a key regulator of ciliogenesis. Although there are well-documented examples of E3 ubiquitin ligases and deubiquitases in the regulation of cilia proteins, many putative components remain unvalidated. This review explores current understanding of how the UPS influences primary cilia formation, and also how recent screen data have identified more putative regulators of the UPS. Emerging research has identified many promising leads in the search for regulators of this important organelle and may identify potential novel therapeutic targets for intervention in cancer and other disease contexts.

scholarly journals The Primary Cilium as a Hedgehog Signal Transduction Machine

2009 ◽  
pp. 199-222 ◽  
Author(s):  
Sarah C. Goetz ◽  
Polloneal J.R. Ocbina ◽  
Kathryn V. Anderson
Keyword(s):  
Signal Transduction ◽  
Primary Cilium ◽  
Hedgehog Signal Transduction ◽  
Hedgehog Signal

scholarly journals Scube activity is necessary for Hedgehog signal transduction in vivo

2012 ◽  
Vol 368 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Jacque-Lynne F.A. Johnson ◽  
Thomas E. Hall ◽  
Jennifer M. Dyson ◽  
Carmen Sonntag ◽  
Katie Ayers ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Hedgehog Signal Transduction ◽  
Hedgehog Signal

scholarly journals Cholesterol Metabolism Is Required for Intracellular Hedgehog Signal Transduction In Vivo

PLoS Genetics ◽  
2011 ◽  
Vol 7 (9) ◽  
pp. e1002224 ◽  
Author(s):  
Rolf W. Stottmann ◽  
Annick Turbe-Doan ◽  
Pamela Tran ◽  
Lisa E. Kratz ◽  
Jennifer L. Moran ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cholesterol Metabolism ◽  
Hedgehog Signal Transduction ◽  
Hedgehog Signal

scholarly journals Infection, dissemination, and transmission efficiencies of Zika virus in Aedes aegypti after serial passage in mosquito or mammalian cell lines or alternating passage in both cell types

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lourdes G. Talavera-Aguilar ◽  
Reyes A. Murrieta ◽  
Sungmin Kiem ◽  
Rosa C. Cetina-Trejo ◽  
Carlos M. Baak-Baak ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Cell Lines ◽  
Zika Virus ◽  
Cell Types ◽  
Mosquito Cell ◽  
Cell Passage ◽  
Genetic Changes ◽  
Synonymous Substitutions ◽  
Vertebrate Cell

Abstract Background Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) with an urban transmission cycle that primarily involves humans and Aedes aegypti. Evidence suggests that the evolution of some arboviruses is constrained by their dependency on alternating between disparate (vertebrate and invertebrate) hosts. The goals of this study are to compare the genetic changes that occur in ZIKV after serial passaging in mosquito or vertebrate cell lines or alternate passaging in both cell types and to compare the replication, dissemination, and transmission efficiencies of the cell culture-derived viruses in Ae. aegypti. Methods An isolate of ZIKV originally acquired from a febrile patient in Yucatan, Mexico, was serially passaged six times in African green monkey kidney (Vero) cells or Aedes albopictus (C6/36) cells or both cell types by alternating passage. A colony of Ae. aegypti from Yucatan was established, and mosquitoes were challenged with the cell-adapted viruses. Midguts, Malpighian tubules, ovaries, salivary glands, wings/legs and saliva were collected at various times after challenge and tested for evidence of virus infection. Results Genome sequencing revealed the presence of two non-synonymous substitutions in the premembrane and NS1 regions of the mosquito cell-adapted virus and two non-synonymous substitutions in the capsid and NS2A regions of both the vertebrate cell-adapted and alternate-passaged viruses. Additional genetic changes were identified by intrahost variant frequency analysis. Virus maintained by continuous C6/36 cell passage was significantly more infectious in Ae. aegypti than viruses maintained by alternating passage and consecutive Vero cell passage. Conclusions Mosquito cell-adapted ZIKV displayed greater in vivo fitness in Ae. aegypti compared to the other viruses, indicating that obligate cycling between disparate hosts carries a fitness cost. These data increase our understanding of the factors that drive ZIKV adaptation and evolution and underscore the important need to consider the in vivo passage histories of flaviviruses to be evaluated in vector competence studies. Graphic abstract "Image missing"

The mechanism of hedgehog signal transduction

2005 ◽  
Vol 33 (6) ◽  
pp. 1509 ◽  
Author(s):  
D. Kalderon
Keyword(s):  
Signal Transduction ◽  
Hedgehog Signal Transduction ◽  
Hedgehog Signal
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