Related Experiment Video
Updated: Aug 13, 2026

Imaging Mitochondrial Ca2+ Uptake in Astrocytes and Neurons using Genetically Encoded Ca2+ Indicators (GECIs)
Published on: January 22, 2022
PACAP support of neuronal survival requires MAPK- and activity-generated signals
Phyllis C Pugh1, Joseph F Margiotta
1Department of Neurosciences, Medical University of Ohio, 3035 Arlington Avenue, Toledo, OH 43614, USA. ppugh@meduohio.edu
Abstract:
Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed in the parasympathetic ciliary ganglion (CG) and modulates nicotinic acetylcholine receptor function. PACAP also provides trophic support, promoting partial survival of CG neurons in culture and full survival when accompanied by membrane depolarization. We probed the adenylate cyclase (AC) and phospholipase-C (PLC) transduction cascades stimulated by PACAP to determine their respective roles in supporting neuronal survival and examined their interaction with signals generated by membrane activity. While PLC-dependent signaling was dispensable, AC-generated signals proved critical for PACAP to support neuronal survival. Specifically, PACAP-supported survival was mimicked by 8Br-cAMP and blocked by inhibiting either PKA or the phosphorylation of mitogen-activated protein kinase (MAPK). The ability of PACAP to promote survival was additionally dependent on spontaneous activity as blocking Na+ or Ca2+ channel currents completely abrogated trophic effects. Our results underscore the importance of coordinated MAPK- and activity-generated signals in transducing neuropeptide-mediated parasympathetic neuronal survival.
Related Concept Videos
MAPK Signaling Cascades
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Mitogens and the Cell Cycle
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway
