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

ACTIS DATO VIRGINIA; JALDIN-FINCATI J; VAZQUEZ MM; BONACCI GR; SANCHEZ MC; CHIABRANDO GA

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

SAIB

Macroglobulinproteasecomplex (α2M*) is a LRP1 ligand, which internalizes by endocytosis and degrades in lysosomes. α2M* alsoinduces the LRP1 trafficking to plasma membrane (PM) through non-characterized exocytic route. Glucosetransporter type 4 (GLUT4) is an insulin-regulated glucose transporter expressed in adipose and muscle cells, whichis stored in specialized GLUT4 storage vesicles (GSVs). Insulin stimulation induces GSVs traffic to PM byexocytosis, with increased GLUT4 expression and glucose uptake at cell surface level. The failure of GLUT4 trafficis involved in Type 2 Diabetes Mellitus. LRP1 is the main protein component of GSVs, although its function in thesevesicles is not completely understood. Herein we study if LRP1 and GLUT4 share the same exocytic route in HeLaand MIO-M1 cells cultured in the presence of α2M* (60 nM) or insulin (100 nM) at different times at 37 °C. Byconfocal microscopy we found LRP1 and GLUT4 colocalization in intracellular vesicles suggesting GSVs in bothtypes of cells. By biotin-labeling protein assay, we showed that LRP1 translocates to PM with α2M*or insulin. Theα2M*-induced LRP1 traffic was abolished by PD98059 but not by LY294002. These results suggest that α2M* andinsulin induce the LRP1 sorting to PM by different exocytic routes.