VPS34 is a PI3K that is involved in endolysosomal and cellular processes, such as vesicle trafficking and metabolism. New findings now demonstrate that VPS34 also influences important endocytic, transport and metabolic processes in the kidney proximal tubule — a region that is important for transport and metabolic functions.

To better understand the role of VPS34 in the proximal tubule, Markus Rinschen and colleagues generated mice with inducible, tubule-specific deletion of VPS34. The mice were viable but demonstrated indices of kidney dysfunction, associated with some structural anomalies and alterations in the localization of proximal-tubule endocytic receptors. Proteomic analyses revealed a decrease in the abundance of nutrient transporters and in proteins of the retromer complex — a key component of the endosomal protein-sorting machinery. These changes were associated with a reduction in gluconeogenesis and a corresponding increase in β-oxidation and glutamine metabolism.

Credit: D. Johnston/Springer Nature Limited

The researchers also noted a decrease in the abundance of apically located virus receptors, such as ACE2, in the knockout mice. Moreover, inhibition of VPS34 suppressed the ability of SARS-CoV-2 to infect human kidney organoids and cultured proximal-tubule cells. The authors say their work highlights functions of VS34 that may be important in the context of viral and metabolic disease.