Nonmuscle myosin 2 proteins encoded by Myh9 , Myh10 , and Myh14 are uniquely distributed in the tubular segments of murine kidney

Abstract

The diverse epithelial cell types of the kidneys are segregated into nephron segments and the collecting ducts in order to endow each tubular segment with unique functions. The rich diversity of the epithelial cell types is highlighted by the unique membrane channels and receptors expressed within each nephron segment. Our previous work identified a critical role for Myh9 and Myh10 in mammalian endocytosis. Here, we examined the expression patterns of Nonmuscle myosin 2 (NM2) heavy chains encoded by Myh9, Myh10, and Myh14 in mouse kidneys as these genes may confer unique nephron segment‐specific membrane transport properties. Interestingly, we found that each segment of the renal tubules predominately expressed only two of the three NM2 isoforms, with isoform‐specific subcellular localization, and different levels of expression within a nephron segment. Additionally, we identify Myh14 to be restricted to the intercalated cells and Myh10 to be restricted to the principal cells within the collecting ducts and connecting segments. We speculate that the distinct expression pattern of the NM2 proteins likely reflects the diversity of the intracellular trafficking machinery present within the different renal tubular epithelial segments.

Single Cell Profiling of Acute Kidney Injury Reveals Novel Transcriptional Signatures, Mixed Identities and Epithelial-to-Stromal Crosstalk

“…As both scRNAseq and CISH indicated, UIR caused a marked Myh9 elevation in all renal tubule compartments, including the sub-clusters of injured and dedifferentiated proximal tubules, and in the collecting ducts ( Figures 5D and 5E). Importantly, previous work specifically reported that Myh9 expression is absent in normal proximal tubules (Otterpohl et al, 2017). We validated the injured proximal tubule expression via co-staining the Myh9 CISH with Aqp1 IF and identified Aqp1-positive proximal tubules exhibiting elevated Myh9 expression which was not detected in the control ( Figure 5F), providing an additional evidence for the injury induced mesenchymal phenotype in renal epithelial tubules.…”

Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease

“…Conditional genetic inactivation of Myh9 (NM2A) and Myh10 (NM2B) in adult mouse renal epithelia results in progressive kidney disease. MYH9&10 proteins have a partially overlapping expression pattern in murine tubular epithelial segments (15). In order to uncover redundant functions of NM2 proteins in the kidney epithelial compartments, as well as to model a severe loss-of-function phenotype, we inactivated both alleles of Myh9 and Myh10 only in the adult renal epithelium.…”

“…Loss of MYH9&10 proteins in mouse renal tubules results in intracellular accumulation of glycosylphosphatidylinositol-anchored protein UMOD and gradual loss of NKCC2 in the TAL. MYH9 (NM2A) and MYH10 (NM2B) are both expressed in the mouse TAL segment (15); therefore, we assessed the localization and expression pattern of the major TAL-specific membrane-associated proteins. UMOD is a unique glycosylphosphatidylinositol-anchored (GPI-anchored) protein in the TAL segment that undergoes N-glycosylation(s) and as a mature protein has a 16-to 24-hour turnover rate on the apical membrane (22).…”

“…These observations establish cell type-specific role(s) for NM2 proteins in regulation of specialized renal epithelial transport pathways and reveal the possibility that human kidney disease associated with MYH9 mutations could be of renal epithelial origin. murine renal tubular segments (15). Taken together, we hypothesized that the NM2 proteins have unique, cell type-specific role(s) in regulating the renal epithelial transport machinery.…”

Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based Chemotherapy

“…Importantly, MYH14 encodes for a heavy chain that is an integral component of nonmuscle myosin 2, a protein essential for kidney development and function (44,45). When evaluated in mice, Myh14 was expressed throughout most segments of the renal tubules, and was implicated in the regulation of the renal epithelial transport process (46). Because cisplatin is excreted from the body predominantly through renal clearance, the importance of genetic architecture surrounding kidney development and function is apparent, and could markedly influence long-term platinum kinetics and circulation in serum.…”