PDE4DIP/Myomegalin as a Golgi-Centrosome Scaffold in Compartmentalized Signaling, Microtubule Organization, and Disease-Associated Pathway Remodeling.
- 1Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, Beijing, China.
- 2National Clinical Research Center for Geriatric Diseases, Beijing, Beijing, China.
Abstract
PDE4DIP/Myomegalin was originally identified as a Golgi- and centrosome-associated protein that interacts with phosphodiesterase 4D, but subsequent work has placed it within a broader network of organelle-associated signaling and cytoskeletal regulation. This review examines PDE4DIP/Myomegalin as a coiled-coil-rich scaffold linking compartmentalized cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, Golgi-centrosome organization, microtubule architecture, and disease-associated pathway remodeling. At the centrosome, long PDE4D-binding myomegalin forms retain PDE4D3 and restrict local PKA activity, thereby influencing Hedgehog signaling. At the Golgi, AKAP9/AKAP450 provides a major scaffold, while selected myomegalin forms support Golgi-derived microtubule organization and endoplasmic reticulum-Golgi trafficking. In KRAS-mutant colorectal cancer models, PDE4DIP promotes tumor growth and MEK inhibitor resistance through Golgi-associated NF1/RAS pathway remodeling. In non-small cell lung cancer, PDE4DIP cooperates with AKAP9 to maintain Golgi localization and stability of PKA regulatory subunit II alpha; PDE4DIP loss activates PKA/cAMP response element-binding protein signaling and suppresses tumor growth. Cardiovascular studies link myomegalin isoform 4 to sarcomeric PKA signaling, co-occurring PDE4DIP and DES variants to conduction phenotypes, and PDE4DIP dysregulation to left ventricular noncompaction-associated cellular changes, although the evidence remains context dependent. Neurological and retinal disease associations remain largely exploratory. Recent work links a PDE4DIP-AKAP9 interaction to cytoskeletal integrity and RAS-ERK/AKT signaling in podocyte injury. Overall, PDE4DIP/Myomegalin is best understood as an organelle-associated organizer whose effects depend on the experimentally reported form, binding partners, and subcellular address rather than on a single linear pathway.
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BibTeX
@article{wang2026pde4dipmyomegalin,
title = {{PDE4DIP/Myomegalin as a Golgi-Centrosome Scaffold in Compartmentalized Signaling, Microtubule Organization, and Disease-Associated Pathway Remodeling.}},
author = {Cong Wang and Chunjing Bian and Zhe Wang and Tao Luo},
journal = {Cell biochemistry and function},
year = {2026},
month = oct,
doi = {10.1002/cbf.70325},
url = {https://europepmc.org/article/MED/42895117},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - PDE4DIP/Myomegalin as a Golgi-Centrosome Scaffold in Compartmentalized Signaling, Microtubule Organization, and Disease-Associated Pathway Remodeling.
AU - Cong Wang
AU - Chunjing Bian
AU - Zhe Wang
AU - Tao Luo
PY - 2026
DA - 2026/10/01
JO - Cell biochemistry and function
DO - 10.1002/cbf.70325
UR - https://europepmc.org/article/MED/42895117
AB - PDE4DIP/Myomegalin was originally identified as a Golgi- and centrosome-associated protein that interacts with phosphodiesterase 4D, but subsequent work has placed it within a broader network of organelle-associated signaling and cytoskeletal regulation. This review examines PDE4DIP/Myomegalin as a coiled-coil-rich scaffold linking compartmentalized cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, Golgi-centrosome organization, microtubule architecture, and disease-associated pathway remodeling. At the centrosome, long PDE4D-binding myomegalin forms retain PDE4D3 and restrict local PKA activity, thereby influencing Hedgehog signaling. At the Golgi, AKAP9/AKAP450 provides a major scaffold, while selected myomegalin forms support Golgi-derived microtubule organization and endoplasmic reticulum-Golgi trafficking. In KRAS-mutant colorectal cancer models, PDE4DIP promotes tumor growth and MEK inhibitor resistance through Golgi-associated NF1/RAS pathway remodeling. In non-small cell lung cancer, PDE4DIP cooperates with AKAP9 to maintain Golgi localization and stability of PKA regulatory subunit II alpha; PDE4DIP loss activates PKA/cAMP response element-binding protein signaling and suppresses tumor growth. Cardiovascular studies link myomegalin isoform 4 to sarcomeric PKA signaling, co-occurring PDE4DIP and DES variants to conduction phenotypes, and PDE4DIP dysregulation to left ventricular noncompaction-associated cellular changes, although the evidence remains context dependent. Neurological and retinal disease associations remain largely exploratory. Recent work links a PDE4DIP-AKAP9 interaction to cytoskeletal integrity and RAS-ERK/AKT signaling in podocyte injury. Overall, PDE4DIP/Myomegalin is best understood as an organelle-associated organizer whose effects depend on the experimentally reported form, binding partners, and subcellular address rather than on a single linear pathway.
SN - 0263-6484
SN - 1099-0844
ER -