Prominin-2 is a novel marker of distal tubules and collecting ducts of the human and murine kidney

Abstract

Prominin-1 (CD133) and its paralogue, prominin-2, are pentaspan membrane glycoproteins that are strongly expressed in the kidney where they have been originally cloned from. Previously, we have described the localization of prominin-1 in proximal tubules of the nephron. The spatial distribution of prominin-2, however, has not yet been documented in the kidney. We therefore examined the expression of this molecule along distinct tubular segments of the human and murine nephron using in situ hybridization and immunohistochemistry. Our findings indicated that human prominin-2 transcripts and protein were confined to distal tubules of the nephron including the thick ascending limb of Henle's loop and the distal convoluted tubule, the connecting duct and to the collecting duct system. Therein, this glycoprotein was enriched at the basolateral plasma membrane of the tubular epithelial cells with exception of the thick ascending limb where it was also found in the apical domain. This is in contrast with the exclusive apical localization of prominin-1 in epithelial cells of proximal nephron tubules. The distribution of murine prominin-2 transcripts was reminiscent of its human orthologue. In addition, a marked enrichment in the epithelium covering the papilla and in the urothelium of the renal pelvis was noted in mice. Finally, our biochemical analysis revealed that prominin-2 was released into the clinically healthy human urine as a constituent of small membrane vesicles. Collectively our data show the distribution and subcellular localization of prominin-2 within the kidney in situ and its release into the urine. Urinary detection of this protein might offer novel diagnostic approaches for studying renal diseases affecting distal segments of the nephron.

Prominin‐1 (CD133) modulates the architecture and dynamics of microvilli

“…The absence of other major symptoms in patients or phenotypes of Prom‐1 null mice can be explained, at least in part, by an upregulation of prominin‐2 in tissues where both molecules are expressed. This is not the case in the retina …”

Hypoxia modulates the undifferentiated phenotype of human renal inner medullary CD133+progenitors through Oct4/miR-145 balance

“…Cells, cultured until confluence on chamberslides coated with fibronectin (Sigma), were fixed in 4% paraformaldehyde containing 2% sucrose for 15 min at 4°C and, when needed, permeabilized with 0.1% Triton X-100 (Sigma) for 8 min at 4°C and then incubated overnight at 4°C with the appropriate antibodies. Indirect immunofluorescence on 10-m cryostatic sections of human kidney was performed following the protocol described by Jászai et al (18). Briefly, sections were incubated with 0.005% SDS in 0.2% gelatin-PBS for 30 min.…”

Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis

“…Both prominins have been shown to directly bind cholesterol and associate with membrane microdomains in living cells [13,14,15]. Prom1 (CD133) has been widely studied as a marker for certain stem cells and cancer stem cells [5,12,16], whereas Prom2 has been shown to be present in some epithelial cells but is otherwise little studied [11,17,18]. The prominins have been proposed to be involved in the organization of membrane protrusions but the specific function of these proteins is presently unknown [5,11].…”