ALPHA-2 MACROGLOBULIN/LRP1 SYSTEM REGULATES THE MT1-MMP ACTIVITY IN RETINAL GLIAL MÜLLER CELLS.

BARCELONA PF; JALDIN-FINCATI J; CHIABRANDO GA; SANCHEZ MC

San Luis

Otro; 47 Reunion Anual de SAIB; 2011

M¨¹ller cells (MC) undergoes functional and morphological changes during retinal proliferative disorders. Previously, we demonstrated that MC express the ¦Á2-Macroglobulin (¦Á2M) receptor, LRP1, and that under ¦Á2M treatment, MC regulate the MMP-2 activity and MC migration on different matrix-protein-coated surfaces by a LRP1-dependent mechanism, which suggest the participation of MT1-MMP. Herein, we evaluated whether LRP1 regulates the MT1-MMP function in MC stimulated by ¦Á2M. The MIO-M1 cell line was used. The cellular distribution of MT1-MMP and LRP1 was examined by confocal microscopy using GFP-conjugated MT1-MMP and specific antibodies against LRP1 and intracellular compartments. The molecular association of MT1-MMP/LRP1 was analyzed by immunoprecipitation (IP). MIO-M1 cells under ¦Á2M 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 ¦Á2M stimulation. These results demonstrate that MT1-MMP is associated with LRP1 at intracellular level in MIO-M1 cells stimulated by ¦Á2M, which suggest that this receptor is regulating the intracellular traffic of MT1-MMP to the plasma membrane under ¦Á2M stimulation in MC.