CDC42 is a member of Rho GTPase family that regulates various biological processes and its activity can be hijacked by invading pathogens. Here, we discovered that the level of active CDC42 in hepatocytes positively correlates with the entry capacity of hepatitis B virus (HBV). Mechanistically, CDC42 activation effectively promotes the transport of the viral receptor sodium taurocholate co-transporting polypeptide (NTCP) to the plasma membrane via Rab11 dependent recycling endosomal pathway. NTCP interacts with Rab11 and activation of CDC42 signaling reinforces the interaction between NTCP and Rab11. We further show that clathrin mediated endocytosis (CME), the known HBV entry pathway, is independent of CDC42 activity. Intriguingly, we reveal that CDC42 dependent macropinocytosis is a route for HBV entry, which is equally essential for viral infection as CME. Together, our findings uncover new mechanisms for HBV entry that involve unrecognized functions of CDC42 and suggest that Rho GTPase signaling might represent a potential target for antiviral therapy.
Understanding the absorption of natural polysaccharides is crucial for advancing their development and application. However, their oral absorption mechanisms and potential applications remain unclear. In this study, Astragalus homogeneous polysaccharide (APS3a) was isolated and characterized. Based on the structural analysis, in vitro and in vivo tracking of APS3a was conducted using FITC- and Cy7 amine labeling to investigate its transport and absorption mechanisms. The results indicated that APS3a can traverse the intestinal mucus layer and is mainly absorbed in the jejunum, subsequently distributing gradually to the liver and kidneys. Further investigation of its transport mechanism revealed that APS3a undergoes energy-dependent active transport, utilizing transcellular transport pathways such as caveolin-mediated endocytosis, macropinocytosis, and sodium-glucose cotransporter 1 (SGLT1)-mediated endocytosis. Additionally, APS3a has the capacity to reversibly open tight junction proteins, facilitating transport through the paracellular transport pathway. Moreover, APS3a can function as an excipient, self-assembling with flavonoids from Astragalus Radix to form complexes, thereby enhancing the permeability and absorption of these flavonoids. These findings provide valuable insights into the oral absorption of APS3a and its potential applications, which are significant for the development and application of polysaccharides.
危险品化学品经营许可证（带存储）