Skip to main content
Journal cover image

Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base.

Publication ,  Journal Article
Barzi, M; Berenguer, J; Menendez, A; Alvarez-Rodriguez, R; Pons, S
Published in: J Cell Sci
January 1, 2010

Cerebellar granular neuronal precursors (CGNPs) proliferate in response to the mitogenic activity of Sonic hedgehog (Shh), and this proliferation is negatively regulated by activation of cAMP-dependent protein kinase (PKA). In the basal state, the PKA catalytic subunits (C-PKA) are inactive because of their association with the regulatory subunits (R-PKA). As the level of cAMP increases, it binds to R-PKA, displacing and thereby activating the C-PKA. Here we report that, in the presence of Shh, inactive C-PKA accumulates at the cilium base of proliferative CGNPs whereas removal of Shh triggers the activation of PKA at this particular location. Furthermore, we demonstrate that the anchoring of the PKA holoenzyme to the cilium base is mediated by the specific binding of the type II PKA regulatory subunit (RII-PKA) to the A-kinase anchoring proteins (AKAPs). Disruption of the interaction between RII-PKA and AKAPs inhibits Shh activity and, therefore, blocks proliferation of CGNP cultures. Collectively, these results demonstrate that the pool of PKA localized to the cilium base of CGNP plays an essential role in the integration of Shh signal transduction.

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Cell Sci

DOI

EISSN

1477-9137

Publication Date

January 1, 2010

Volume

123

Issue

Pt 1

Start / End Page

62 / 69

Location

England

Related Subject Headings

  • Stem Cells
  • Signal Transduction
  • Protein Transport
  • Protein Subunits
  • Protein Binding
  • Mice
  • Hedgehog Proteins
  • Enzyme Activation
  • Developmental Biology
  • Cyclic AMP-Dependent Protein Kinases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Barzi, M., Berenguer, J., Menendez, A., Alvarez-Rodriguez, R., & Pons, S. (2010). Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base. J Cell Sci, 123(Pt 1), 62–69. https://doi.org/10.1242/jcs.060020
Barzi, Mercedes, Jordi Berenguer, Anghara Menendez, Ruben Alvarez-Rodriguez, and Sebastian Pons. “Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base.J Cell Sci 123, no. Pt 1 (January 1, 2010): 62–69. https://doi.org/10.1242/jcs.060020.
Barzi M, Berenguer J, Menendez A, Alvarez-Rodriguez R, Pons S. Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base. J Cell Sci. 2010 Jan 1;123(Pt 1):62–9.
Barzi, Mercedes, et al. “Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base.J Cell Sci, vol. 123, no. Pt 1, Jan. 2010, pp. 62–69. Pubmed, doi:10.1242/jcs.060020.
Barzi M, Berenguer J, Menendez A, Alvarez-Rodriguez R, Pons S. Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base. J Cell Sci. 2010 Jan 1;123(Pt 1):62–69.
Journal cover image

Published In

J Cell Sci

DOI

EISSN

1477-9137

Publication Date

January 1, 2010

Volume

123

Issue

Pt 1

Start / End Page

62 / 69

Location

England

Related Subject Headings

  • Stem Cells
  • Signal Transduction
  • Protein Transport
  • Protein Subunits
  • Protein Binding
  • Mice
  • Hedgehog Proteins
  • Enzyme Activation
  • Developmental Biology
  • Cyclic AMP-Dependent Protein Kinases