Nanoparticles Internalization through HIP-55-Dependent Clathrin Endocytosis Pathway.

Nanoparticles are promising tools for biomedicine. Many nanoparticles are internalized to function. Clathrin-mediated endocytosis is one of the most important mechanisms for nanoparticle internalization. However, the regulatory mechanism of clathrin-mediated nanoparticle endocytosis is still unclear. Here, we report that the adapter protein HIP-55 regulates clathrin-mediated nanoparticle endocytosis. CdSe/ZnS quantum dots (QDs), a typical nanoparticle, enter cells through the HIP-55-dependent clathrin endocytosis pathway. Both pharmacological inhibitor and genetic intervention demonstrate that QDs enter cells through clathrin-mediated endocytosis. HIP-55 can interact with clathrin and promote clathrin-mediated QDs endocytosis. Furthermore, HIP-55 ΔADF which is defective in F-actin binding fails to promote QDs endocytosis, indicating HIP-55 promotes clathrin-mediated QDs endocytosis depending on interaction with F-actin. In vivo, HIP-55 knockout also inhibits endocytosis of QDs. These findings reveal that HIP-55 acts as an intrinsic regulator for clathrin-mediated nanoparticle endocytosis, providing new insight into the nanoparticle internalization and a new strategy for nanodrug enrichment in target cells.

Src mediates ß-adrenergic receptor induced YAP tyrosine phosphorylation.

The Hippo pathway is a newly identified pathway and evolutionarily conserved from flies to humans mainly regulating cell proliferation. Transcriptional co-activator Yes-associated protein (YAP) functions as a major downstream effector and key node of the Hippo pathway. Phosphorylation of YAP is critical to regulate YAP activity and its corresponding functions. ß-adrenergic receptor (ß-AR), a typical G protein coupled receptor (GPCR), mediates proliferation in various cell types and regulates multiple physical and pathological processes. However, the role of ß-AR in regulating YAP remains elusive. Here, we report that ß-AR can obviously stimulate YAP tyrosine phosphorylation. The mechanism is that ß-AR stimulation results in tyrosine kinase Src activation and Src phosphorylates YAP tyrosine at Y357. Further studies demonstrate that inhibition of Src kinase activity can obviously alleviate ß-AR induced YAP tyrosine phosphorylation and cell proliferation. We conclude that ß-AR can induce YAP tyrosine phosphorylation and also establish the Src/YAP pathway as a critical signaling branch downstream of GPCR.