Ariable, non-a helical N-terminal head and 370-86-5 cost C-terminal tail domains that contain several phosphorylation sites. MedChemExpress PS 1145 vimentin monomers associate in parallel to form a coiled-coil dimer, and the degree of assembly/ disassembly of vimentin into filament polymers is regulated by the dephosphorylation/phosphorylation status of the vimentin head and tail domains [31]. In other words, dephosphorylation induces vimentin IF assembly, and phosphorylation induces disassembly. There are a number of other post-translational modifications of vimentin as well, including citrullination, sumoylation, and OGlcNac derivatization, all of which can affect vimentin structure and function [32]. Attempts to define specific physiologic functions for vimentin through gene targeting were originally inconclusive, as vimentin knockout mice did not demonstrate an overt phenotype [33]. Later, however, vimentin knockouts were shown to have glial abnormalities causing cerebellar and motor coordination deficits [34], and impaired wound healing reflecting delayed fibroblast migration and decreased wound contraction [35]. Other reports showed that vimentin knockouts display reductions in lymphocyte binding to endothelial cells and less vascular transmigration due toVimentin and Integrins in Alport GlomeruliFigure 5. Integrin a3 protein is upregulated in podocytes of Alport glomeruli. A : Fresh frozen kidney sections from 4 week old Alport mice were labeled with a combination of rabbit anti-integrin a3 and mouse anti-synaptopodin IgGs, followed by the appropriate species-specific Alexa Fluor secondaries. Anti-integrin a3 immunolabeling (A) is restricted to the epithelial podocyte layer, marked by synaptopodin staining (B), and overlap of staining is shown in C (merge). D : Representative fluorescence micrographs are shown of anti-integrin a3 labeling of wild-type (D, wt), or Alport (E) mouse glomeruli. The glomerular fluorescence intensities were averaged for n = 3 mice of each genotype, wild-type (wt, blue) or Alport (red), and integrin a3 signals were significantly greater in Alport. * p = 0.006. doi:10.1371/journal.pone.0050745.gdecreases in expression of integrin b1 on lymphocytes and ICAM1 and VCAM-1 on endothelial cells [36]. The relatively abundant presence of vimentin in mammalian podocytes has been known for some time [23,37,38]. Vimentin appears to be associated with another IF protein, nestin, in the cell body and primary processes of podocytes, and some studies show an extension of vimentin into the actin microfilament- and microtubule-rich terminal foot processes [24]. Upregulation of vimentin and reorganization of podocyte IFs have also previously been 1317923 observed in rats with puromycin aminonucleoside nephrosis [39,40], mice with podocyte-selective deletion of the microRNA generating enzyme, dicer, which results in podocyte foot process effacement, split GBMs, and proteinuria [41], and in human glomerular diseases [42,43]. The overexpression of vimentin seen here and in the examples cited above is probably related to podocyte shape change that leads to broadening of foot processes during effacement, but may reflect other intracellular activities of vimentin in response to podocyte injury. Among other functions, vimentin is now known as a key regulator of cell adhesion through its direct and indirect interaction with integrins [30]. Integrins mediate cell-cell and cell-extracellular matrix (ECM) interactions and are comprised of non-covalent heterodimers of transmemb.Ariable, non-a helical N-terminal head and C-terminal tail domains that contain several phosphorylation sites. Vimentin monomers associate in parallel to form a coiled-coil dimer, and the degree of assembly/ disassembly of vimentin into filament polymers is regulated by the dephosphorylation/phosphorylation status of the vimentin head and tail domains [31]. In other words, dephosphorylation induces vimentin IF assembly, and phosphorylation induces disassembly. There are a number of other post-translational modifications of vimentin as well, including citrullination, sumoylation, and OGlcNac derivatization, all of which can affect vimentin structure and function [32]. Attempts to define specific physiologic functions for vimentin through gene targeting were originally inconclusive, as vimentin knockout mice did not demonstrate an overt phenotype [33]. Later, however, vimentin knockouts were shown to have glial abnormalities causing cerebellar and motor coordination deficits [34], and impaired wound healing reflecting delayed fibroblast migration and decreased wound contraction [35]. Other reports showed that vimentin knockouts display reductions in lymphocyte binding to endothelial cells and less vascular transmigration due toVimentin and Integrins in Alport GlomeruliFigure 5. Integrin a3 protein is upregulated in podocytes of Alport glomeruli. A : Fresh frozen kidney sections from 4 week old Alport mice were labeled with a combination of rabbit anti-integrin a3 and mouse anti-synaptopodin IgGs, followed by the appropriate species-specific Alexa Fluor secondaries. Anti-integrin a3 immunolabeling (A) is restricted to the epithelial podocyte layer, marked by synaptopodin staining (B), and overlap of staining is shown in C (merge). D : Representative fluorescence micrographs are shown of anti-integrin a3 labeling of wild-type (D, wt), or Alport (E) mouse glomeruli. The glomerular fluorescence intensities were averaged for n = 3 mice of each genotype, wild-type (wt, blue) or Alport (red), and integrin a3 signals were significantly greater in Alport. * p = 0.006. doi:10.1371/journal.pone.0050745.gdecreases in expression of integrin b1 on lymphocytes and ICAM1 and VCAM-1 on endothelial cells [36]. The relatively abundant presence of vimentin in mammalian podocytes has been known for some time [23,37,38]. Vimentin appears to be associated with another IF protein, nestin, in the cell body and primary processes of podocytes, and some studies show an extension of vimentin into the actin microfilament- and microtubule-rich terminal foot processes [24]. Upregulation of vimentin and reorganization of podocyte IFs have also previously been 1317923 observed in rats with puromycin aminonucleoside nephrosis [39,40], mice with podocyte-selective deletion of the microRNA generating enzyme, dicer, which results in podocyte foot process effacement, split GBMs, and proteinuria [41], and in human glomerular diseases [42,43]. The overexpression of vimentin seen here and in the examples cited above is probably related to podocyte shape change that leads to broadening of foot processes during effacement, but may reflect other intracellular activities of vimentin in response to podocyte injury. Among other functions, vimentin is now known as a key regulator of cell adhesion through its direct and indirect interaction with integrins [30]. Integrins mediate cell-cell and cell-extracellular matrix (ECM) interactions and are comprised of non-covalent heterodimers of transmemb.
