Work

PACSIN2 deletion impairs transferrin uptake and terminal erythroid maturation in mice

Year: 2026

Type: article

Abstract: Erythropoiesis requires extensive cytoskeletal and membrane remodeling, particularly during terminal differentiation, when erythroblasts undergo chromatin condensation, polarization, and enucleation within erythroblastic islands (EBIs). While several cytoskeletal regulators are established effectors of erythropoiesis, the contribution of membrane-sculpting proteins remains less well defined. Here, we investigated the role of the Fes/CIP4 homology Bin–Amphiphysin–Rvs (F-BAR) protein PACSIN2 in erythropoiesis using Pacsin2 –/– mice. Pacsin2 –/– mice developed mild hypochromic microcytic anemia with preserved red blood cell (RBC) counts and survival, increased resistance to osmotic stress, and splenomegaly. In mature RBCs, PACSIN2 localized as puncta partially overlapping with filamentous actin (F-actin), supporting a role in membrane–cytoskeleton interactions. Spectral flow cytometry revealed expansion of erythroid-biased progenitors, suggesting compensatory adaptation to impaired maturation. Ultrastructural and immunohistochemical analyses demonstrated disrupted EBIs, with Pacsin2 –/– macrophages exhibiting reduced cytoplasmic extensions and fewer phagosomes. Although erythroblast enucleation was preserved, transferrin uptake was impaired in Pacsin2 –/– erythroblasts despite normal CD71 expression, indicating defective clathrin-mediated endocytosis rather than receptor availability. Histological analysis further revealed iron accumulation in splenic red pulp macrophages. Together, the findings implicate PACSIN2 in the membrane remodeling required for transferrin receptor internalization in erythroblasts and demonstrate its contribution to iron acquisition and terminal erythroid maturation.

Source: Blood Red Cells & Iron

DOI: 10.1016/j.brci.2026.100128