HUMAN ERYTHROPOIESIS: MOLECULAR AND CELLULAR STUDY OF LRP1 DURING ERYTHROID MATURATION.

VIEYRA C; CHIABRANDO GA; FADER CM; MORAS M ; LEFEVRE S; SÁNCHEZ MC; OSTUNI M

Salta

Congreso; Joint XIV PABMB Congress and LV Annual SAIB Meeting; 2019

SAIB

Erythroid maturation is a highly regulated process where immature cells from bone marrow go through a series of differentiation stages to become mature red blood cells. During this, essential intracellular modifications take place such as degradation of entire organelles that are non-necessary for erythrocyte functionality. Autophagy is a lysosomal degradative pathway where macromolecules and organelles are surrounded by double-membrane vesicles called autophagosomes and then targeted to lysosomes for its degradation. Autophagy participates actively in erythropoiesis being responsible for engulfment and elimination of mitochondria (mitophagy) and ribosomes once all hemoglobin has been synthesized. Low-density lipoprotein receptor-related protein 1 (LRP1) is a transmembrane receptor involved in a wide range of cellular processes such as proliferation, metabolism, and differentiation. LRP1 participates as a scavenger receptor for hemin-hemopexin complex, leading to its endocytic internalization for metabolism. Previous results from our group demonstrated that hemin, an erythropoiesis inductor, is able to generate an autophagic response (mitophagy) in erythroleukemia cells lines (K562 cells), inducing the expression of LRP1 and some autophagic genes such as LC3, Atg5, and Beclin1. Moreover, we have demonstrated that LRP1is in part responsible for hemin autophagy activation. In this work, we show that LRP1 has an expression peak at day 10 of ex vivo erythropoiesis, being practically undetectable at final maturative stages (reticulocytes and erythrocytes). Similar results were observed by confocal microscopy where there was an increased number of cells labeled with this receptor at day 10 compared with cells at day 0, 7 or 17 of ex vivo maturation. These results suggest that LRP1 has an important role in a specific stage during erythropoiesis. Taken together, our results suggest that LRP1 is favoring erythroid maturation maybe by inducing an autophagic response, being a possible therapeutic candidate that helps in hematopoietic disorders as well as the chronic myelogenous leukemia (CML) treatment.