The role of alpha2M/LRP1 system in the regulation of matrix metalloproteinases in Muller cells

BARCELONA PF; JALDIN-FINCATI JR; SÁNCHEZ MC; CHIABRANDO GA

Potrero de los Funes, San Luis

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2011

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

Müller cells (MC) undergoes changes during retinal proliferative disorders. We have previously demonstrated that MC express the 2-Macroglobulin ( 2M) receptor, LRP1, and that under 2M treatment, MC regulate the MMP-2 activity and MC migration on different matrix-protein-coated surfaces through a LRP1-dependent mechanism, which suggest the participation of MT1-MMP. To test this hypothesis we evaluated whether LRP1 regulates the MT1- MMP function in an spontaneously immortalized Müller cell line (MIO-M1) stimulated by 2M. The cellular distribution of MT1- MMP and LRP1 was examined by confocal microscopy using GFPMT1- MMP and specific antibodies against LRP1 and intracellular compartments of endocytosis and endocytic recycling. The molecular association of MT1-MMP/LRP1 was analyzed by immunoprecipitation (IP). MIO-M1 cells under 2M treatment showed that LRP1 and MT1-MMP were mainly co-localized in endosomal compartments characterized as sorting endosomes. By IP assay we showed a molecular association between MT1-MMP and LRP1, which was increased by 2M stimulation. Results from our experiments provided new knowledge to understand how LRP1 regulates the intracellular traffic of MT1-MMP to the plasma membrane.