Type III-PI3Kinase/Vps34 is crucial for kidney proximal tubules and thyroid structure and functions
(2018)
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- Vesicular trafficking is key for epithelial polarity and function. PI3KC3/Vps34 is the only lipid-kinase directly producing phosphatidylinositol 3-phosphate, which recruits key effectors on endocytic and autophagic membranes and thus controls vesicular trafficking. My thesis addressed its role in kidney proximal tubular cells (PTCs) and thyrocytes, by conditional genetic excision in vivo. Vps34/ PTCs established normal apico-basal polarity, then showed defective apical addressing of transporters and endocytic receptors, resulting into Fanconi-like syndrome. Lysosome mislocalization and abortive autophagic flux led to loss of cellular homeostasis. Vps34/ thyrocytes also showed preserved apico-basal polarity and thyroglobulin secretion into colloid, but defective iodothyroglobulin in most follicles linked to severe hypothyroidism, and impaired autophagy. We concluded that Vps34 is essential for apical vesicular trafficking and homeostasis, thus function, of PTCs and thyrocytes
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Grieco, G. (2018). Type III-PI3Kinase/Vps34 is crucial for kidney proximal tubules and thyroid structure and functions. https://hdl.handle.net/2078.5/125414