**2. Hormonal actions and interactions for regulating protein endocytosis in PTCs**

Receptor-mediated endocytosis is a pivotal function of PTCs through which the cells reabsorb and metabolize proteins (and other substances) from glomerular filtrates (Saito, Sato et al. 2010). This reabsorption process is extremely efficient as urine is virtually proteinfree in humans, and it accounts for the essential conservation of nutrients, carrier-bound vitamins, and trace elements filtered by glomeruli. Impairment of the process results in a loss of such substances and development of proteinuria.

## **2.1 Endocytic receptors involved in protein reabsorption in PTCs**

The two major endocytic receptors expressed at the apical membranes of PTCs are megalin and cubilin (Saito, Sato et al. 2010) which act cooperatively in the uptake of glomerularfiltered proteins and mediate their metabolism in PTCs (Fig. 2).

Some hormones, such as dopamine, renalase, vitamin D3 and klotho, are synthesized in PTCs and others come from other organs. Renalase acts to metabolize dopamine.

AMN, amnionless; FGF23, fibroblast growth factor 23; GLP1, glucagon-like peptide 1; NaPi-IIa, sodiumdependent phosphate cotransporter type IIa; NaPi-IIc, sodium-dependent phosphate cotransporter type IIc; NHE3, Na+/H+ exchanger isoform 3; Pit-2, sodium-dependent phosphate symporter 2; PTC, proximal tubule cell; PTH, parathormone; SGLT2, sodium-glucose cotransporter 2

Fig. 2. Hormonal actions and interactions on the functions of receptors and transporters involved in receptor-mediated protein endocytosis and reabsorption of sodium and phosphate in the apical membrane of PTCs.
