AKAP2/PKA complex coordinates primary ciliogenesis, ciliary trafficking and Shh signaling.
7 affiliations
- 1Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy.
- 2Department of Biology, University of Naples Federico II, Naples, Italy.
- 3Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Italy.
- 4Genome Research Center for Health-CRGS, Campus of Medicine of the University of Salerno, Baronissi, Italy.
- 5Molecular Pathology and Medical Genomics Unit, AOU "S. Giovanni di Dio e Ruggi d'Aragona", University of Salerno, Salerno, Italy.
- 6Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France.
- 7Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy. [email protected].
Abstract
The primary cilium is a sensory organelle present in all eukaryotic cells that acts as a signaling hub that receives, integrates and transmits signals carried out by extracellular stimuli, playing a fundamental role in cell behavior, development and tissue homeostasis. Genetic mutations in genes encoding for structural components and regulators of primary cilium underlie severe developmental defects, also known as ciliopathies. Understanding cilium biology may, thus, provide novel therapeutic strategies for ciliopathies. Here, we report that A-Kinase Anchor protein 2(AKAP2) dynamically localizes within the primary cilium and forms complexes with kinesin motor proteins and components of the intra-flagellar transport system. Genetic deletion experiments and functional analysis demonstrate that AKAP2/PKA complex controls cilium biogenesis and intraciliary trafficking of cargo receptors, acting as a positive regulator of Shh pathway. In the medaka fish model, depletion of AKAP2 affects ciliogenesis and ciliary trafficking, delays embryonic development and significantly increases the embryonic death rate.Our findings identify AKAP2 as a ciliary scaffold protein that finely controls ciliogenesis, intraciliary trafficking and Hedgehog signaling cascade. Manipulating ciliary AKAP2 signaling, thus, provides a new therapeutic window for ciliopathy disorders.
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BibTeX
@article{chiuso2026akap2pka,
title = {{AKAP2/PKA complex coordinates primary ciliogenesis, ciliary trafficking and Shh signaling.}},
author = {Francesco Chiuso and Giuliana Giamundo and Emanuela Senatore and Laura Rinaldi and Francesca Rizzo and Simona Aversano and Antonio Giuseppe Bianco and Alfonso Carleo and Elena Alexandrova and Alessandro Weisz and Jack Brendan Jordan and Iolanda Carratù and Stephane Audebert and Luc Camoin and Maria Chiara Zizolfi and Leandra Sepe and Paolo Maiuri and Luca Lignitto and Ivan Conte and Antonio Feliciello},
journal = {Cell communication and signaling : CCS},
year = {2026},
month = jul,
doi = {10.1186/s12964-026-03092-8},
url = {https://europepmc.org/article/MED/42897536},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - AKAP2/PKA complex coordinates primary ciliogenesis, ciliary trafficking and Shh signaling.
AU - Francesco Chiuso
AU - Giuliana Giamundo
AU - Emanuela Senatore
AU - Laura Rinaldi
AU - Francesca Rizzo
AU - Simona Aversano
AU - Antonio Giuseppe Bianco
AU - Alfonso Carleo
AU - Elena Alexandrova
AU - Alessandro Weisz
AU - Jack Brendan Jordan
AU - Iolanda Carratù
AU - Stephane Audebert
AU - Luc Camoin
AU - Maria Chiara Zizolfi
AU - Leandra Sepe
AU - Paolo Maiuri
AU - Luca Lignitto
AU - Ivan Conte
AU - Antonio Feliciello
PY - 2026
DA - 2026/07/01
JO - Cell communication and signaling : CCS
DO - 10.1186/s12964-026-03092-8
UR - https://europepmc.org/article/MED/42897536
AB - The primary cilium is a sensory organelle present in all eukaryotic cells that acts as a signaling hub that receives, integrates and transmits signals carried out by extracellular stimuli, playing a fundamental role in cell behavior, development and tissue homeostasis. Genetic mutations in genes encoding for structural components and regulators of primary cilium underlie severe developmental defects, also known as ciliopathies. Understanding cilium biology may, thus, provide novel therapeutic strategies for ciliopathies. Here, we report that A-Kinase Anchor protein 2(AKAP2) dynamically localizes within the primary cilium and forms complexes with kinesin motor proteins and components of the intra-flagellar transport system. Genetic deletion experiments and functional analysis demonstrate that AKAP2/PKA complex controls cilium biogenesis and intraciliary trafficking of cargo receptors, acting as a positive regulator of Shh pathway. In the medaka fish model, depletion of AKAP2 affects ciliogenesis and ciliary trafficking, delays embryonic development and significantly increases the embryonic death rate.Our findings identify AKAP2 as a ciliary scaffold protein that finely controls ciliogenesis, intraciliary trafficking and Hedgehog signaling cascade. Manipulating ciliary AKAP2 signaling, thus, provides a new therapeutic window for ciliopathy disorders.
SN - 1478-811X
ER -