Nephron specific knockin of the PIKfyve binding deficient Vac14L156R mutant results in albuminuria and mesangial expansion.

Nephron specific knockin of the PIKfyve binding deficient Vac14L156R mutant results in albuminuria and mesangial expansion. Am J Physiol Renal Physiol. 2018 Aug 01;: Authors: Michgehl U, Skryabin BV, Bayraktar S, Vollenbröker B, Ciarimboli G, Heitplatz B, Van Marck V, Gröne HJ, Pavenstädt H, Weide T Abstract Intracellular trafficking processes play a key role for the establishment and maintenance of membrane surfaces in renal epithelia. Therefore, dysfunctions of these trafficking processes could be key events and important determinants in the onset and progression of diseases. The presence of cellular vacuoles - observed in many histologic analyses of renal diseases - is a macroscopic hint for disturbed intracellular trafficking processes. However, how vacuoles develop and which intracellular pathways are directly affected remains largely unknown. Previous studies showed that in some cases vacuolization is linked to malfunction of the Vac14 complex. This complex regulates intracellular PIP levels, which in turn control the maturation of early into late endosomes as well as the processing of autophagosomes into autophagolysosomes. Here, we analyzed the role of Vac14 in mice and observed that the nephron specific knockin of the PIKfyve-binding deficient Vac14L156R mutant led to albuminuria accompanied by mesangial expansion, increased glomerular size and an elevated expression of several kidney injury markers. Overexpression of thi...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research