Erythroid differentiation is augmented in Reelin‐deficient K562 cells and homozygous reeler mice

Abstract

a b s t r a c tReelin is an extracellular glycoprotein that is highly conserved in mammals. In addition to its expression in the nervous system, Reelin is present in erythroid cells but its function there is unknown. We report in this study that Reelin is up-regulated during erythroid differentiation of human erythroleukemic K562 cells and is expressed in the erythroid progenitors of murine bone marrow. Reelin deficiency promotes erythroid differentiation of K562 cells and augments erythroid production in murine bone marrow. In accordance with these findings, Reelin deficiency attenuates AKT phosphorylation of the Ter119 + CD71+ erythroid progenitors and alters the cell number and frequency of the progenitors at different erythroid differentiation stages. A regulatory role of Reelin in erythroid differentiation is thus defined.

Nonneuronal roles for the reelin signaling pathway

“…Initially, liver cells secreting reelin into the circulation were proposed as the major source of reelin found in the blood plasma (Smalheiser et al, ). Further studies defined RELN as an erythroid‐enriched gene, and confirmed that blood cells, such as erythrocytes and platelets, also produce reelin protein (Jacquel et al, ; Redmond et al, ; Tseng et al, ; Redmond et al, ; Chu et al, ).…”

“…In heterozygous reeler +/‐ mice, levels of circulating reelin are half of those found in wild‐type littermates, and the protein is absent from the plasma of reeler ‐/‐ mice (Smalheiser et al, ). reeler ‐/‐ mice also have higher red blood cell (RBC) counts compared with wild‐type controls, without changes in spleen size (Chu et al, ). Higher RBC numbers are also observed in the reeler ‐/‐ bone marrow, concomitant with attenuation of phosphorylated Akt (Chu et al, ).…”

“…reeler ‐/‐ mice also have higher red blood cell (RBC) counts compared with wild‐type controls, without changes in spleen size (Chu et al, ). Higher RBC numbers are also observed in the reeler ‐/‐ bone marrow, concomitant with attenuation of phosphorylated Akt (Chu et al, ). In addition, reeler ‐/‐ mice display impaired hemostasis, evidenced by prolonged bleeding time and a higher tendency to re‐bleed in bleeding time assays, along with abnormalities in thrombin clot formation (Tseng et al, ).…”

“…The importance of reelin in hemostasis was further demonstrated by studies of the human chronic myelogenous leukemia cell line K562. Treatment of K562 cells with imatinib or sodium butyrate, both of which induce erythroid differentiation, increased expression of RELN mRNA and reelin protein (Jacquel et al, ; Chu et al, ). In line with findings of enhanced erythropoiesis in reeler ‐/‐ mice, knockdown of RELN enhanced erythroid differentiation of K562 cells (Chu et al, ).…”

Neurochemical Markers in the Mammalian Brain: Structure, Roles in Synaptic Communication, and Pharmacological Relevance

“…Reelin mRNA is found in the small intestine, where the epithelium has a high turnover rate and is subject to rapid renewal [218]; reelin is also involved in the processes of osteogenesis and dentinogenesis [219,220]. Moreover, reelin is expressed in hepatic stellate cells of the liver, an organ that is self-regenerative [221,222], along with the blood [221,223], mammary gland [224], and the bovine and chicken endometrium and ovarian follicle [225,226]. Though its exact mechanisms of action in these widespread systems are unclear, the pervasive nature of reelin, despite its large size and the energy required to secrete it, points to a broad but significant role in the development of a diverse set of organs and tissues.…”