Epac2 contributes to PACAP-induced astrocytic differentiation through calcium ion influx in neural precursor cells
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Astrocytes play a critical role in normal brain functions and maintaining the brain microenvironment, and defects in astrocytogenesis during neurodevelopment could give rise to severe mental illness and psychiatric disorders. During neuro- embryogenesis, astrocytogenesis involves astrocytic differentiation of neural precursor cells (NPCs) induced by signals from ciliary neurotrophic factor (CNTF) or pituitary adenylate cyclase-activating peptide (PACAP). However, in contrast to the CNTF signaling pathway, the exact mechanism underlying astrocytic differentiation induced by PACAP is unknown. In the present study, we aimed to verify a signaling pathway specific to PACAP-induced astrocytogenesis, using exchange protein directly activated by cAMP2 (Epac2)-knockout mice. We found that PACAP could trigger astrocytic differentiation of NPCs via Epac2 activation and an increase in the intracellular calcium concentration via a calcium ion influx. Taken together, we concluded that astrocytogenesis stimulated by PACAP occurs through a novel signaling pathway independent from CNTF-JAK/STAT signaling, that is the well-known pathway of astrocytogenesis.
Abstract
Astrocytes play a critical role in normal brain functions and maintaining the brain microenvironment, and defects in astrocytogenesis during neurodevelopment could give rise to severe mental illness and psychiatric disorders. During neuro- embryogenesis, astrocytogenesis involves astrocytic differentiation of neural precursor cells (NPCs) induced by signals from ciliary neurotrophic factor (CNTF) or pituitary adenylate cyclase-activating peptide (PACAP). However, in contrast to the CNTF signaling pathway, the exact mechanism underlying astrocytic differentiation induced by PACAP is unknown. In the present study, we aimed to verify a signaling pathway specific to PACAP-induced astrocytogenesis, using exchange protein directly activated by cAMP2 (Epac2)-knockout mice. We found that PACAP could trigger astrocytic differentiation of NPCs via Epac2 activation and an increase in the intracellular calcium concentration via a calcium ion influx. Taken together, we concluded that astrocytogenesis stimulated by PACAP occurs through a novel signaling pathway independent from CNTF-JAK/STAT signaling, that is the well-known pathway of astrocytogenesis.
참고문헌 (23)
- Wang DD, "The astrocyte odyssey", Prog Neurobiol, 86, pp.342~367 (2008)
- Park JK, "Bipotent cortical progenitor cells process conflicting cues for neurons, glia in a hierarchical manner", J Neurosci, 19, pp.10383~10389 (1999)
- Bonni A, "Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway", Science, 278, pp.477~483 (1997)
- Vaudry D, "Pituitary adenylate cyclase-activating polypeptide, its receptors:20 years after the discovery", Pharmacol Rev, 61, pp.283~357 (2009)
- Breckler M, "Rap-linked cAMP signaling Epac proteins: compartmentation, functioning, disease implications", Cell Signal, 23, pp.1257~1266 (2011)
- Gloerich M, "Epac: defining a new mechanism for cAMP action", Annu Rev Pharmacol Toxicol, 50, pp.355~375 (2010)
- Grandoch M, "The role of Epac proteins, novel cAMP mediators, in the regulation of immune, lung, neuronal function", Br J Pharmacol, 159, pp.265~284 (2010)
- Lee K, "Involvement of cAMP-guanine nucleotide exchange factor II in hippocampal long-term depression, behavioral flexibility", Mol Brain, 8, pp.38~ (2015)
- Fernandes HB, "Epac2Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus", J Neurosci, 35, pp.6544~6553 (2015)
- Cebolla B, "DREAM mediates cAMP-dependent, Ca2＋-induced stimulation of GFAP gene expression, regulates cortical astrogliogenesis", J Neurosci, 28, pp.6703~6713 (2008)
- Brini M, "Neuronal calcium signaling: function, dysfunction", Cell Mol Life Sci, 71, pp.2787~2814 (2014)
- Tsai TD, "Imaging of caffeine-inducible release of intracellular calcium in cultured embryonic mouse telencephalic neurons", J Neurobiol, 27, pp.252~265 (1995)
- Vallejo M, "PACAP signaling to DREAM: a cAMP- dependent pathway that regulates cortical astrogliogenesis", Mol Neurobiol, 39, pp.90~100 (2009)
- Srivastava DP, "Social, communication, , cortical structural impairments in Epac2-deficient mice", J Neurosci, 32, pp.11864~11878 (2012)
- Yang Y, "EPAC null mutation impairs learning, social interactions via aberrant regulation of miR-124, Zif268 translation", Neuron, 73, pp.774~788 (2012)
- Sandau US, "Astrocyte-specific disruption of SynCAM1 signaling results in ADHD-like behavioral manifestations", PLoS One, 7, pp.e36424~ (2012)
- Morgan JT, "Stereological study of amygdala glial populations in adolescents, adults with autism spectrum disorder", PLoS One, 9, pp.e110356~ (2014)
- Richardson PM, "Ciliary neurotrophic factor: a review", Pharmacol Ther, 63, pp.187~198 (1994)
- Teh DB, "Regulation of later neurogenic stages of adult-derived neural stem", progenitor cells by L-type Ca2＋ channels, 2014, pp.56, 583~594
- Glaser T, "Modulation of mouse embryonic stem cell proliferation, neural differentiation by the P2X7 receptor", PLoS One, 9, pp.e96281~ (2014)
- Payet MD, "PAC1 receptor activation by PACAP-38 mediates Ca2＋ release from a cAMP-dependent pool in human fetal adrenal gland chromaffin cells", J Biol Chem, 278, pp.1663~1670 (2003)
- 엄선애, "Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson’s disease", BMB Reports, 48(7), pp.395~400 (2015), 생화학분자생물학회
- Xi Lu, "The SH2 domain is crucial for function of Fyn in neuronal migration and cortical lamination", BMB Reports, 48(2), pp.97~102 (2015), 생화학분자생물학회