LRP-1 TRAFFICKING IS MODIFIED BY HEMIN IN ERYTHROLEUKEMIA CELLS

GROSSO R; SANCHEZ MC; CHIABRANDO GA; COLOMBO M; FADER KAISER C

Congreso; LI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015

induces erythroid cell differentiation but the molecular and cellular mechanisms involved in this process are stilldebated. The transmembrane low density lipoprotein receptor related protein 1 (LRP1), is the scavenger for thehemin-hemopexine complex that allows its internalization. Autophagy is a lysosomal-degradative process necessaryfor the final erythroid differentiation, leading to the degradation of non necessary organelles. Our objective was toelucidate the role of hemin-autophagy induction in LRP1 gene expression and trafficking. To determine these, weperformed qRT-PCR in hemin-stimulated k562 cells. Interestingly, hemin caused an increased level of LRP1 andautophagic genes (i.e. MAP1a1b, Beclin1, Atg5). Moreover, to characterize the distribution of this receptor, differentendosomal markers as Rab5, Rab7, LBPA and lysotrakcer were tested by inmunofluorescence. Confocal imaging hasshown that LRP1 is mainly localized in autofagosomes (LC3 positive structures), late endosomes and lysosomalstructures under hemin conditions. In general our results suggest that hemin induces autophagy, enhancing LRP1 andautophagic gene expression. Likewise, hemin would be targeting the LRP1 receptor to degradative compartiments,regulating its amount and activity.