Mechanisms of aquaporin ‐4 vesicular trafficking in mammalian cells

In this study, we explored molecular mechanisms of AQP4 trafficking in mammalian cells. AQP4 continuously cycles between the cell surface, Rab5-positive early and Rab11-positive recycling endosomes in mammalian cells. AQP4 internalisation is dynamin-dependent and AQP4 translocation mechanisms are impaired upon inhibition of Rab5 and Rab11 function as well as cytoskeleton dynamics revealing potential targets for oedema treatment. Created withbiorender.com. AbstractThe aquaporin-4 (AQP4) water channel is abundantly expressed in the glial cells of the central nervous system and facilitates brain swelling following diverse insults, such as traumatic injury or stroke. Lack of specific and therapeutic AQP4 inhibitors highlights the need to explore alternative routes to control the water permeability of glial cell membranes. The cell surface abundance of AQP4 in mammalian cells fluctuates rapidly in response to changes in oxygen levels and tonicity, suggesting a role for vesicular trafficking in its translocation to and from the cell surface. However, the molecular mechanisms of AQP4 trafficking are not fully elucidated. In this work, early and recycling endosomes were investigated as likely candidates of rapid AQP4 translocation together with changes in cytoskeletal dynamics. In transiently transfected HEK293 cells a significant amount of AQP-eGFP colocalised with mCherry-Rab5-positive early endosomes and mCherry-Rab11-positive recycling endosomes. When exposed to hypotonic conditi...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research