Megalin-mediated albumin endocytosis in cultured murine mesangial cells. 2020

Mark A Bryniarski, and Benjamin M Yee, and Lee D Chaves, and Corrine M Stahura, and Rabi Yacoub, and Marilyn E Morris
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, 303 Pharmacy Building, Buffalo, NY, 14214, USA.

Endocytosis by podocytes is gaining increased attention as a biologic means of removing large proteins such as serum albumin from the glomerular barrier. Some of this function has been attributed to the megalin/cubilin (Lrp2/Cubn) receptor complex and the albumin recycling protein FcRn (Fcgrt). However, whether other glomerular cells possess the potential to perform this same phenomenon or express these proteins remains uncharacterized. Mesangial cells are uniquely positioned in glomeruli and represent a cell type capable of performing several diverse functions. Here, the expression of megalin and FcRn in murine mesangial cells along with the megalin adaptor protein Dab-2 (Dab2) was shown for the first time. Cubilin mRNA expression was detected, but the absence of the cubilin partner amnionless (Amn) suggested that cubilin is minimally functional, if at all, in these cells. Mesangial cell endocytosis of albumin was characterized and shown to involve a receptor-mediated process. Albumin endocytosis was significantly impaired (p < 0.01) under inducible megalin knockdown conditions in stably transduced mesangial cells. The current work provides both the novel identification of megalin and FcRn in mesangial cells and the functional demonstration of megalin-mediated albumin endocytosis.

UI MeSH Term Description Entries
D011961 Receptors, Fc Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules. Fc Receptors,Fc Receptor,Receptor, Fc
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004705 Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis. Endocytoses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012710 Serum Albumin, Bovine Serum albumin from cows, commonly used in in vitro biological studies. (From Stedman, 25th ed) Fetal Bovine Serum,Fetal Calf Serum,Albumin Bovine,Bovine Albumin,Bovine Serum Albumin,Albumin, Bovine,Albumin, Bovine Serum,Bovine Serum, Fetal,Bovine, Albumin,Calf Serum, Fetal,Serum, Fetal Bovine,Serum, Fetal Calf
D015395 Histocompatibility Antigens Class I Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells. Class I Antigen,Class I Antigens,Class I Histocompatibility Antigen,Class I MHC Protein,Class I Major Histocompatibility Antigen,MHC Class I Molecule,MHC-I Peptide,Class I Histocompatibility Antigens,Class I Human Antigens,Class I MHC Proteins,Class I Major Histocompatibility Antigens,Class I Major Histocompatibility Molecules,Human Class I Antigens,MHC Class I Molecules,MHC-I Molecules,MHC-I Peptides,Antigen, Class I,Antigens, Class I,I Antigen, Class,MHC I Molecules,MHC I Peptide,MHC I Peptides,Molecules, MHC-I,Peptide, MHC-I,Peptides, MHC-I
D048868 Adaptor Proteins, Signal Transducing A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes Signal Transducing Adaptor Proteins
D050527 Mesangial Cells Smooth muscle-like cells adhering to the wall of the small blood vessels of the KIDNEY at the glomerulus and along the vascular pole of the glomerulus in the JUXTAGLOMERULAR APPARATUS. They are myofibroblasts with contractile and phagocytic properties. These cells and their MESANGIAL EXTRACELLULAR MATRIX constitute the GLOMERULAR MESANGIUM. Glomerular Mesangial Cells,Extraglomerular Mesangial Cells,Lacis Cells,Mesangial Cells, Kidney,Renal Glomerulus Mesangial Cells,Renal Mesangial Cells,Cell, Extraglomerular Mesangial,Cell, Glomerular Mesangial,Cell, Kidney Mesangial,Cell, Lacis,Cell, Mesangial,Cell, Renal Mesangial,Cells, Extraglomerular Mesangial,Cells, Glomerular Mesangial,Cells, Kidney Mesangial,Cells, Lacis,Cells, Mesangial,Cells, Renal Mesangial,Extraglomerular Mesangial Cell,Glomerular Mesangial Cell,Kidney Mesangial Cell,Kidney Mesangial Cells,Lacis Cell,Mesangial Cell,Mesangial Cell, Extraglomerular,Mesangial Cell, Glomerular,Mesangial Cell, Kidney,Mesangial Cell, Renal,Mesangial Cells, Extraglomerular,Mesangial Cells, Glomerular,Mesangial Cells, Renal,Renal Mesangial Cell
D051017 Apoptosis Regulatory Proteins A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES. Anti-Apoptotic Protein,Anti-Apoptotic Proteins,Apoptosis Inducing Protein,Apoptosis Inhibiting Protein,Apoptosis Regulatory Protein,Pro-Apoptotic Protein,Pro-Apoptotic Proteins,Programmed Cell Death Protein,Apoptosis Inducing Proteins,Apoptosis Inhibiting Proteins,Death Factors (Apoptosis),Programmed Cell Death Proteins,Survival Factors (Apoptosis),Anti Apoptotic Protein,Anti Apoptotic Proteins,Inducing Protein, Apoptosis,Inducing Proteins, Apoptosis,Inhibiting Protein, Apoptosis,Inhibiting Proteins, Apoptosis,Pro Apoptotic Protein,Pro Apoptotic Proteins,Protein, Anti-Apoptotic,Protein, Apoptosis Inducing,Protein, Apoptosis Inhibiting,Protein, Apoptosis Regulatory,Protein, Pro-Apoptotic,Proteins, Anti-Apoptotic,Proteins, Apoptosis Inducing,Proteins, Apoptosis Inhibiting,Proteins, Pro-Apoptotic,Regulatory Protein, Apoptosis,Regulatory Proteins, Apoptosis

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