The phosphoinositides signal transduction pathway in astrocytes

Signal transduction from plasma membrane to cell nucleus is a complex process depending on various components including lipid signaling molecules. Phosphoinositides (PI) constitute an important signaling system. Enzymes related to the PI signal transduction pathway may act at cell periphery, plasma membrane or nuclear level. The PI cycle was also hypothesized to be involved in neuronal as well as glial activities. Many evidences support the hypothesis that the PI cycle is involved in astrocytes activation during the neurodegeneration process. Phosphoinositide-specific phospholipase C (PI-PLC) family of enzymes is crucial in PI signaling system. In fact, PI-PLC enzymes regulate the spatial and temporal balance of PI. Thirteen mammalian PI-PLC isoforms were identified, divided into six sub-families on the basis of amino acid sequence, domain structure and mechanism of recruitment in response to activated receptors: β(1–4), γ(1, 2), δ(1, 3, 4), ϵ(1), ζ(1), and η(1-2). Different expression of the isoforms was described in pathological cells with respect to the corresponding normal counterparts. The expression panel of PI-PLC isoforms varies under different conditions, such as tumoral progression or inflammatory activation, with respect to the quiescent astrocytes counterpart. These observations suggest that in the nervous system the fine regulation of PI-PLC isoforms play a role in the activation of the glia and in the inflammation processes.