Fig. 4: Role of PIPn signaling in regulating microtubule dynamics.
From: Phosphoinositide signaling at the cytoskeleton in the regulation of cell dynamics
The schematic illustrates the interplay between activated receptors at the cell membrane, endocytosis, PIPn signaling, and microtubule dynamics. Receptor activation generates various PIPns (e.g., PtdIns3P, PtdIns(4,5)P2, PtdIns(3,4,5)P3) at endosomes, driving the recruitment and activation of AKT, which promotes cellular proliferation, migration, and invasion. Within this process, endosomal PtdIns3P recruits class I PI3K components (p110α/p85) by binding to the C2 domain of p110α. This complex is further linked to microtubules through interactions between MAP4 and PI3K. In cancer cells, the switch of the PI3K regulatory subunit from p85α to p85β enhances binding to PtdIns3P, amplifying complex recruitment and promoting constitutive PI3K/AKT signaling. At the microtubule-organizing centers (centrosomes), an accumulation of PtdIns4P occurs, where it interacts with TTBK2 and the accessory factor CEP164, preventing their interaction and inhibiting the removal of microtubule capping protein CP110 and microtubule extension. PIPKIγ reduces PtdIns4P levels by phosphorylating it to PtdIns(4,5)P2, which promotes TTBK2 recruitment and microtubule polymerization. In contrast, dephosphorylation of PtdIns(4,5)P2 back to PtdIns4P by INPP5E reverses this effect. This diagram is generated using BioRender.
