Abstract
Purinergic receptors participate, in almost every cell type, in controlling metabolic activities and many physiological functions including signal transmission, proliferation and differentiation. While most of P2Y receptors induce transient elevations of intracellular calcium concentration by activation of intracellular calcium pools and forward these signals as waves which can also be transmitted into neighboring cells, P2X receptors produce calcium spikes which also include activation of voltage-operating calcium channels. P2Y and P2X receptors induce calcium transients that activate transcription factors responsible for the progress of differentiation through mediators including calmodulin and calcineurin. Expression of P2X2 as well as of P2X7 receptors increases in differentiating neurons and glial cells, respectively. Gene expression silencing assays indicate that these receptors are important for the progress of differentiation and neuronal or glial fate determination. Metabotropic receptors, mostly P2Y1 and P2Y2 subtypes, act on embryonic cells or cells at the neural progenitor stage by inducing proliferation as well as by regulation of neural differentiation through NFAT translocation. The scope of this review is to discuss the roles of purinergic receptor-induced calcium spike and wave activity and its codification in neurodevelopmental and neurodifferentiation processes.
Highlights
Purinergic receptors participate, in almost every cell type, in controlling metabolic activities and many physiological functions including signal transmission, proliferation and differentiation
intracellular calcium signaling (ICS) is impressively diverse and consists of mechanisms that differ in frequency, amplitude and spatio-temporal patterning depending on an extensive molecular repertoire of signaling components
Similar patterns of spike activity were observed in neural tube stages in vivo [2,7] and during neuronal differentiation of embryonal carcinoma (CSC, a model for pluripotent embryonic stem cells) and adult bone marrow mesenchymal stem cells [8,9]
Summary
ICS is an important issue to study because of its versatility, which controls different cell processes essential for cellular function, including stem cell differentiation. P2X and P2Y purinergic receptors promote proliferation by a mechanism in which ATP induces increases in [Ca2+]i in form of waves or spikes, leading to activation of various effectors, followed by an alteration in transcription factor expression and activity patterns such as CREB, NFAT and MEF2, which are involved in stimulation of neural gene transcription. Better understanding of these processes will establish the importance of purinergic signaling in stem cell biology.
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