Enhanced podocyte vesicle transport in the nephrotic rat

Abstract

Albumin endocytosis is enhanced in the podocytes of minimal change nephrotic syndrome. We investigated that the endocytic vesicle transport in the podocyte using three-dimensional observation in a rat model of puromycin aminonucleoside (PAN)-induced nephrotic syndrome. At day 7, Evans Blue-labeled albumin was intravenously injected in PAN rats, and one kidney was fixed for a morphological analysis; the other was used for the isolation of glomeruli through sieving and protein analyses. Evans Blue-labeled albumin was found to accumulate in an increased number of vesicles in the podocytes of PAN rat. Continuous sections and its three-dimensional observation demonstrated that vesicles may be transported from the cytoplasm to the apical membrane of the podocytes. The increased protein bands in the gel electrophoresis of the sieved glomeruli of nephrotic rats were analyzed by mass spectrometry in comparison to the control rats. The major proteins increased in the nephrotic rats were cytoplasmic dynein 1 heavy chain, myosin IX, and myosin VIIb. In conclusion, the podocyte endocytic vesicles carrying albumin increased with glomerular cytoplasmic dynein and myosin in minimal change nephrotic rats.

Mechanism Underlying Selective Albuminuria in Minimal Change Nephrotic Syndrome

“…Recent emerging evidence supports the notion of albumin transport through the podocyte cell body [26, 27, 30, 32, 35]. In 1955, Rinehart proposed that the glomerular filtrate is transported across the glomerular epithelial cytoplasm via small vesicles [36].…”

“…In 1955, Rinehart proposed that the glomerular filtrate is transported across the glomerular epithelial cytoplasm via small vesicles [36]. Large numbers of endocytic vesicles have been detected in the podocytes of MCNS patients by TEM [35, 37, 38]. Furthermore, a numerous holes have been observed at the basal and apical surface of podocytes [27, 39], suggesting endocytosis and exocytosis of transported proteins (Figure 5).…”

“…In neuronal axonal transport, kinesin-1 mediates the anterograde transport of synaptic vesicles, secretory vesicles, and mitochondria, whereas cytoplasmic dynein retrogradely transports cargo such as injured signaling endosomes, lysosomes, lipid droplets, and mitochondria from axonal lesion sites toward the soma along microtubules [40, 41]. Interestingly, an analysis of glomerular proteins by mass spectrometry revealed that levels of motor proteins including cytoplasmic dynein 1, myosin IXa (Myo9a), and myosin VIIb were increased in PAN-induced nephrotic rats compared with control rats [35]. As the minus end of the microtubule connects with the adherens junction, which is located below the tight junction of podocytes with foot process effacement, and cytoplasmic dynein 1 carries endocytosed vesicles toward the minus ends of microtubules, cytoplasmic dynein 1 will transport vesicles from the basal membrane to the apical membrane of podocytes (Figure 6).…”

Peer Review #2 of "Overexpression of Myo1e promotes albumin endocytosis by mouse glomerular podocytes mediated by Dynamin (v0.2)"

“…Manuscript to be reviewed injury. There are several pathways of albumin endocytosis, such as Dynamin-dependent podocyte endocytosis, FcRn-mediated albumin transcytosis (Kinugasa et al 2011), clathrinmediated endocytosis (Soda et al 2012), caveolin-mediated endocytosis (Dobrinskikh et al 2014), fluid phase-endocytosis (Palm et al 2015) and dynein-microtubule related vesicle transport (Tojo et al 2017). Dynamin plays a crucial role in maintaining the structure and function of the glomerular filtration barrier.…”

Peer Review #2 of "Overexpression of Myo1e promotes albumin endocytosis by mouse glomerular podocytes mediated by Dynamin (v0.1)"

“…Our findings showed that overexpression of Myo1e promoted apoptosis of MPC5 cells that were co-cultured with BSA, indicating that overexpression of Myo1e may induce podocyte injury. There are several pathways of albumin endocytosis, such as Dynamin-dependent podocyte endocytosis, FcRn-mediated albumin transcytosis (Kinugasa et al 2011), clathrinmediated endocytosis (Soda et al 2012), caveolin-mediated endocytosis (Dobrinskikh et al 2014), fluid phase-endocytosis (Palm et al 2015) and dynein-microtubule related vesicle transport (Tojo et al 2017). Dynamin plays a crucial role in maintaining the structure and function of the glomerular filtration barrier.…”