Figure 1.

Diagram of the regulation of macropinocytosis by PI3K, DAG, Wnt/β-catenin, GSK3, APC, and Axin1 from the literature and the present paper

PI3K activated by RTKs or G-protein coupled receptors leads to the generation of PIP3 in the plasma membrane, which triggers the formation of macropinocytic cups by the actin cytoskeletal machinery network. PIP3 activates PLCγ and is itself converted into DAG, which in turn activates PKC which is required for cup closure and completion of macropinocytosis.²⁶ In the lower part of the diagram, Wnt signaling, through its Frizzled (Fzd) and LRP6 receptors, inhibits a destruction complex containing GSK3, APC, and Axin1 by translocating it into MVBs. In the absence of Wnt, GSK3 normally suppresses macropinocytosis.²⁹ LiCl, used in this study, induces macropinocytosis by inhibiting GSK3. Exogenous DAG (purple oval) increases Wnt signaling by sequestration of the GSK3/APC/Axin1 destruction complex.