CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
INSULIN REGULATES THE LRP1 TRANSLOCATION TO THE CELL SURFACE IN MÜLLER GLIAL CELLS
Autor/es:
VAZQUEZ MAXIMILIANO; BONACCI, GUSTAVO; CHIABRANDO, GUSTAVO; ACTIS DATO VIRGINIA; BARCELONA, PABLO; FADER, CLAUDIO M; GUTIERREZ VICTORIA; SANCHEZ CECILIA
Lugar:
Parana
Reunión:
Congreso; LIV Reunion Anual SAIB 2018; 2018
Institución organizadora:
SOCIEDAD ARGENTINA DE INVESTIGACION EN BIOQUIMICA Y BIOLOGIA CELULAR
Resumen:
Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) is an endocytic and signaling receptor expressed in retinal Müller glial cells(MGCs). This receptor regulates the molecular activity of different membrane proteins, included insulin receptor (IR), which is involved with theMGC motility and metabolism. Moreover, insulin increases the LRP1 expression in the cell surface of neurons and hepatic cells, although theintracellular route of this LRP1 sorting in these cells and MGCs is not well established. Hence, in the present work we investigate the insulin-induced LRP1 translocation to the plasma membrane in human retinal MGC-derived cell line, MIO-M1. By electron microscopy we observedthat LRP1 is stored in small vesicles (mean diameter range of 100?120 nm), which were positive for sortilin and VAMP2, and also incorporatedGLUT4 when it was transiently transfected. Next, by biotin-labeling protein assay we observed that the LRP1 translocation to the plasmamembrane was promoted by insulin-regulated exocytosis through intracellular activation of the IR/PI3K/Akt axis and Rab-GTPase proteins, suchas Rab8A and Rab10. Moreover, these Rab-GTPases regulated both the constitutive and insulin-induced LRP1 translocation to the plasmamembrane. Finally, we found that dominant-negative Rab8A and Rab10 mutants impaired insulin-induced intracellular signaling of theIR/PI3K/Akt axis, suggesting that these GTPase proteins as well as LRP1 cell surface level are involved in insulin-induced IR activation. Wepropose that insulin-induced LRP1 translocation to the plasma membrane is essential for IR activity, which might be relevant for the function ofMGCs during pathological disorders of the retina associated with insulin resistance.