Fig. 1.

The signalling pathways connected to autophagy. Phosphatidylinositol signalling pathway is regulated by Class I phosphoinositide 3-kinases (PI3Ks), which are activated by kinase receptors like insulin receptors (IR) and responsible for the production of phosphatidylinositol (3,4,5)-triphosphate (PIP3) from phosphatidylinositol 4,5-bisphosphate (PIP2). Phospholipase C (PLC) cleaves the PIP2 into diacyl glycerol and inositol 1,4,5-trisphosphate (IP3). Inositol polyphosphate 1-phosphatase (IPPase) catalyses inositol bisphosphate (IP2) to inositol monophosphate (IP), which is further dephosphorylated by inositol monophosphatase (IMPase) to inositol. High-affinity inositol transport is additionally catalysed by the active myo-inositol/H+ transporter (MIT). MIT, IPPase and IMPase are all inhibited by carbamazepine (CBZ), valproic acid (VPA) and lithium (Li+). PI3Ks have been linked to an extraordinarily diverse group of cellular functions through regulation of the Akt/TSC1-TSC2/mTOR pathway. Disrupted in Schizophrenia 1 (DISC1) in its wild-type form also negatively regulates both GSK3β and Akt (also known as Protein Kinase B, PKB). Tuberous sclerosis protein 1 and 2 (TSC1/2) form a complex that like rapamycin (Rap) inhibits mammalian target of rapamycin kinase (mTOR). Wnt signalling activation is mediated through binding of a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the protein Dishevelled (Dsh). Dsh negatively regulates glycogen synthase kinase-3 beta (GSK3β), which alternatively inhibits β-catenin, one of the central proteins of the Wnt signalling pathway. β-catenin, however, negatively regulates LKB1/AMPK pathway (liver kinase B1/5' adenosine monophosphate-activated protein kinase) that indirectly regulates autophagy.