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Nerve growth factor increases connexin43 phosphorylation and gap junctional intercellular communication
Paul Cushing1, Ruchi Bhalla, Andrew M Johnson
1Department of Anatomy and Cell Biology, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Canada.
Journal of Neuroscience Research
|November 23, 2005
Summary
Nerve growth factor (NGF) enhances gap junction communication in neurons by phosphorylating connexin43 (Cx43) via the MAPK pathway. This neurotrophic regulation offers a new mechanism for controlling neuronal communication during development and repair.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Gap junction function is modulated by connexin phosphorylation.
- Nerve growth factor's (NGF) impact on gap junction function remains unclear.
- Connexin phosphorylation is critical for channel function, trafficking, and degradation.
Purpose of the Study:
- To investigate the effect of NGF on gap junction function in a neuronal model.
- To identify the signaling pathways involved in NGF-mediated regulation of connexin43 (Cx43).
Main Methods:
- Utilized PC12 cells engineered to express Cx43 as a neuronal model.
- Employed immunoblot analysis to detect Cx43 and ERK-1/2 phosphorylation.
- Assessed gap junction intercellular communication using fluorescence recovery after photobleaching (FRAP).
Main Results:
- NGF treatment induced phosphorylation of Cx43 and ERK-1/2 in PC12-Cx43 cells.
- Phosphorylation was mediated by TrkA activation and blocked by the MEK-1/2 inhibitor U0126.
- NGF increased gap junction communication, an effect reversed by U0126.
Conclusions:
- Demonstrated a direct link between neurotrophins (NGF) and connexin phosphorylation via the MAPK pathway.
- Showed that NGF increases gap junctional intercellular communication.
- Highlighted neurotrophic regulation of connexin activity as a novel mechanism for neuronal communication in development and repair.