INTRACELLULAR TRAFFIC OF LRP1 AND GLUT4 IN ALPHA2- MACROGLOBULIN-STIMULATED MIO-M1 CELLS

ACTIS DATO V; JALDIN-FINCATI JR; BONACCI GR; SÁNCHEZ MC; CHIABRANDO GA

ROSARIO, SANTA FE

Congreso; L Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2014

SAIB

CB-P11
INTRACELLULAR TRAFFIC OF LRP1 AND GLUT4 IN ALPHA2- MACROGLOBULIN-STIMULATED MIO-M1 CELLS Actis-Dato V, Jaldín-Fincati JR, Bonacci GR, Sánchez MC, Chiabrando GA. Dep Bioquímica Clínica (CIBICI- CONICET) Facultad Ciencias Químicas Universidad Nacional de Córdoba. E-mail: vickyactisdato@gmail.com Low density lipoprotein receptor-related protein 1 (LRP1) is an endocytic and signaling receptor, which binds alpha 2-macroglobulin-protease complex (α2M*) and promotes cell migration of Muller glial-derived cell line, MIO-M1. The α2M* induces LRP1 translocation to plasma membrane (PM) by two possible pathways; i) Rab11-dependent recycling route, and ii) exocytosis from LRP1-stored vesicles and Rab11-independent pathway, which can be also stimulated by insulin. Glucose transporter type 4 (GLUT4) is a insulin-regulated glucose transporter found in adipose and muscle tissues. Specialized GLUT4 storage vesicles (GSV) can be translocated to PM by insulin through a Rab10-dependent pathway, increasing the glucose uptake. The failure of GLUT4 translocation is involved in insulin resistance and type 2 diabetes mellitus. LRP1 is the main protein component of GSV, although its function is not completely understood. To examine whether α2M* induces GSV translocation to PM, we have characterized the subcellular localization of LRP1 and GLUT4 in MIO-M1 cells. By confocal microscopy and biotin-labeling protein assay we determine that LRP1 and GLUT4 shown a high colocalization in intracellular vesicles, compatible with GSV, and LRP1 was translocated to PM by α2M*, which was unaffected by the presence of a dominant-negative Rab11. We conclude that α2M* induced LRP1 traffic to PM from GSV.