DIFFERENTIAL INTRACELLULAR TRAFFIC OF LRP1 INDUCED BY ALPHA 2-MACROGLOBULIN AND INSULIN

ACTIS-DATO V; JALDIN-FINCATI JR; VAZQUEZ M; BONACCI G; SANCHEZ MC; CHIABRANDO G.

Mar del Plata, Buenos Aires

Congreso; LI Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2015

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Low density lipoprotein receptor-related 1 (LRP1) is an endocytic and signaling receptor. Alpha 2-Macroglobulin protease complex (α2M*) is a LRP1 ligand, which internalizes by endocytosis and degrades in lysosomes. α2M* also induces the LRP1 trafficking to plasma membrane (PM) through non-characterized exocytic route. Glucose transporter type 4 (GLUT4) is an insulin-regulated glucose transporter expressed in adipose and muscle cells, which is stored in specialized GLUT4 storage vesicles (GSVs). Insulin stimulation induces GSVs traffic to PM by exocytosis, with increased GLUT4 expression and glucose uptake at cell surface level. The failure of GLUT4 traffic is involved in Type 2 Diabetes Mellitus. LRP1 is the main protein component of GSVs, although its function in these vesicles is not completely understood. Herein we study if LRP1 and GLUT4 share the same exocytic route in HeLa and MIO-M1 cells cultured in the presence of α2M* (60 nM) or insulin (100 nM) at different times at 37 °C. By confocal microscopy we found LRP1 and GLUT4 colocalization in intracellular vesicles suggesting GSVs in both types of cells. By biotin-labeling protein assay, we showed that LRP1 translocates to PM with α2M*or insulin. The α2M*-induced LRP1 traffic was abolished by PD98059 but not by LY294002. These results suggest that α2M* and insulin induce the LRP1 sorting to PM by different exocytic routes.