The nuclear architectural protein HMGA1a triggers receptor-mediated endocytosis.
High mobility group proteins A (HMGA), nuclear architectural factors, locate in the cell nuclei and mostly execute gene-regulation function. However, our results reveal that a HMGA member (HMGA1a) has a unique plasma membrane receptor; this receptor specifically binds to HMGA-decorated species, effectively mediates endocytosis, and internalizes extracellular HMGA-functionalized cargoes. Indeed, dyes or nanoparticles labeled with HMGA1a protein readily enter Hela cells. Using a stratagem chemical cross-linker, we covalently bonded the HMGA receptor to the HMGA1a-GFP fusion protein, thus capturing the plasma membrane receptor. Subsequent Western blots and SDS-PAGE gel revealed that the HMGA receptor is a 26-kDa protein. Confocal live-cell microscopic imaging was used to monitor the whole endocytic process, in which the internalized HMGA1a-decorated species are transported by motor proteins on microtubules and eventually arrive at the late endosomes/lysosomes. Cell viability assays also suggested that extracellular HMGA1a protein directly influences the survival ability of Hela cells in a dose-dependent manner, implying versatility of HMGA1a protein and its potent role to suppress cancer cell survivability and to regulate growth.
Wu
Wuwei
W
Department of Chemistry and Center for Materials Research, Washington State University, Pullman, Washington 99164, USA.
Wan
Wei
W
Li
Alexander D Q
AD
D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D049452:Green Fluorescent Proteins / Q000737:chemistry; D025741:HMGA1a Protein / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D003432:Cross-Linking Reagents; D011993:Recombinant Fusion Proteins; D025741:HMGA1a Protein; D049452:Green Fluorescent Proteins