RECEPTOR-MEDIATED ENDOCYTOSIS IN KIDNEY PROXIMAL TUBULES - RECENT ADVANCES AND HYPOTHESIS

Preparation of kidney proximal tubules in suspension allows the study of receptor-mediated endocytosis, protein reabsorption, and traffic of endosomal vesicles. The study of tubular protein transport in vitro c oupled with that of the function of endosomal preparation offers a uni que opportunity to investigate a receptor-mediated endocytosis pathway under physiological and pathological conditions. We assume that recep tor-mediated endocytosis of albumin in kidney proximal tubules in situ and in vitro can be regulated, on the one hand, by the components of tile acidification machinery (V-type H+-ATPase, Cl--channel and Na+/H-exchanger), giving rise to formation and dissipation of a proton grad ient in endosomal vesicles, and, on the other hand, by small GTPases o f the ADP-ribosylation factor (Arf)-family. In this paper we thus anal yze the recent advances of the studies of cellular and molecular mecha nisms underlying the identification, localization, and function of the acidification machinery (V-type H+-ATPase, Cl--channel) as well as Ar f-family small GTPases and phospholipase D n the endocytotic pathway o f kidney proximal tubules. Also, we explore the possible functional in teraction between the acidification machinery and Arf-family small GTP ases. Finally, we propose the hypothesis of the regulation of transloc ation of Arf-family small GTPases by an endosomal acidification proces s and its role during receptor-mediated endocytosis in kidney proximal tubules. The results of this study will not only enhance our understa nding of the receptor-mediated endocytosis pathway in kidney proximal tubules under physiological conditions but will also have important im plications with respect to the functional consequences under some path ological circumstances. Furthermore, it may suggest novel targets and approaches in the prevention and treatment of various diseases (cystic fibrosis, Dent's disease, diabetes and autosomal dominant polycystic kidney disease).