Golga7 deletion in hematopoietic cells delays CD71 clearance and impairs erythropoietic recovery under hemolytic stress
TL;DR
Functional assays showed that Golga7 deficiency delayed cell-surface CD71 clearance and prolonged intracellular transferrin retention without detectably affecting erythroid enucleation ex vivo without affecting erythroid recovery under hemolytic stress.
Abstract
Terminal erythropoiesis requires dynamic membrane remodeling and trafficking, but the molecular regulation of these processes remains poorly understood. In this study, we identify GOLGA7, a predominantly Golgi-resident protein, as a regulator of CD71 clearance in reticulocytes and the erythropoietic response to hemolytic stress. Mice with hematopoietic-specific Golga7 deletion exhibited an increased proportion of CD71-positive circulating erythroid cells at steady state, while under hemolytic stress, they showed prolonged CD71 retention, delayed hematological recovery, and increased mortality. Multi-omic analyses of Golga7 deficient bone marrow erythroid cells revealed transcriptomic and proteomic alterations associated with vesicular trafficking. Functional assays showed that Golga7 deficiency delayed cell-surface CD71 clearance and prolonged intracellular transferrin retention without detectably affecting erythroid enucleation ex vivo. These findings highlight the contribution of GOLGA7 to terminal erythroid maturation and effective erythropoietic recovery under hemolytic stress.