L-Ferritin Binding to Scara5: A New Iron Traffic Pathway Potentially Implicated in Retinopathy

Abstract

Iron is essential in the retina because the heme-containing enzyme guanylate cyclase modulates phototransduction in rods and cones. Transferrin endocytosis is the classical pathway for obtaining iron from the blood circulation in the retina. However, the iron storage protein ferritin has been also recently proposed as an iron carrier. In this study, the presence of Scara5 and its binding to L-ferritin was investigated in the retina. Our results showed that Scara5, the specific receptor for L-ferritin, was expressed in mouse and human retinas in many cell types, including endothelial cells. Furthermore, we showed that intravenously injected ferritin crossed the blood retinal barrier through L-ferritin binding to Scara5 in endothelial cells. Thus, suggesting the existence of a new pathway for iron delivery and trafficking in the retina. In a murine model of photoreceptor degeneration, Scara5 was downregulated, pointing out this receptor as a potential player implicated in retinopathy and also as a possible therapeutic target.

Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin

“…To choose suitable cells for mice xenograft studies, two prostate cancer cell lines, LNCaP and 22RV1, were evaluated based on their ability to bind and internalize APODOX-anti-PSMA (prostate-specific membrane antigen). As cellular uptake of APO through either transferrin receptor 1 (TfR) 22 , T cell immunoglobulin and mucin domain-containing protein-2 (TIM-2) 23 or scavenger receptor class A member 5 (SCARA5) 22 is based on this heavy and light chain subunit ratio, their expression was tested. Figure 1a shows the expression profiles of TfR, SCARA5 and PSMA as the most probable preferential targets for APODOX-anti-PSMA binding, as well as the results from Affi-assay, evaluating the binding of APODOX-anti-PSMA to 84 kDa PSMA protein.…”

“…Their quartenary structure is formed by 24 subunits with various ratios of heavy (H-, 21 kDa) and light (L-, 19 kDa) chain. Based on this H-/L-chain ratio, APO can enter cells via TfR (for H-chain APO) 22 , TIM-2 (for H-chain APO) 42 , 43 or SCARA5 (for L-chain APO) 22 , 44 , 45 , although some works have mistakenly identified TfR as the main receptor for both H- and L-chain APO 46 – 48 .…”

Iron Homeostasis in Healthy Kidney and its Role in Acute Kidney Injury

“…For example, L-ferritin−bound iron can be taken up when it binds to Scara5, a protein expressed in the kidney stroma. 21,22 As iron travels along the length of the nephron, it is reabsorbed using other iron transporters such as DMT1, Zrt-and Irt-like protein 8 (ZIP8), and ZIP14. [23][24][25] DMT1 is expressed in the cortex and not in the medulla, and is present at the brush border and apical pole of epithelial cells of proximal tubules.…”

Ellipticine-loaded apoferritin nanocarrier retains DNA adduct-based cytochrome P450-facilitated toxicity in neuroblastoma cells

“…Apoferritin (Apo) is a naturally occurring iron-storage protein consisting of 24 protein subunits responsible for the storage and transfer of iron (Gallois et al, 1997;Kim et al, 2011;Kilic et al, 2012;Tmejova et al, 2013;Blazkova et al, 2013;Heger et al, 2014) that provides much needed properties of a drug-nanocarrier. Various ferritins are internalized by transferrin receptor 1 (TfR1) or scavenger receptor class A member 5 (SCARA5), overexpressed on membranes of some tumor cells (Mendes-Jorge et al, 2014). This can enable natural active targeting to those tumor cells, while passive targeting to tumor tissues is facilitated by the size of the ferritins (Blazkova et al, 2014;Heger et al, 2014).…”