Limits...
The importance of podocyte adhesion for a healthy glomerulus.

Lennon R, Randles MJ, Humphries MJ - Front Endocrinol (Lausanne) (2014)

Bottom Line: The GBM is a dense network of secreted, extracellular matrix (ECM) components and contains tissue-restricted isoforms of collagen IV and laminin in addition to other structural proteins and ECM regulators such as proteases and growth factors.The specialized niche of the GBM provides a scaffold for endothelial cells and podocytes to support their unique functions and human genetic mutations in GBM components lead to renal failure, thus highlighting the importance of cell-matrix interactions in the glomerulus.Cells adhere to ECM via adhesion receptors, including integrins, syndecans, and dystroglycan and in particular the integrin heterodimer α3β1 is required to maintain barrier integrity.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester , Manchester , UK ; Institute of Human Development, Faculty of Medical and Human Sciences, The University of Manchester , Manchester , UK ; Department of Paediatric Nephrology, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK.

ABSTRACT
Podocytes are specialized epithelial cells that cover the outer surfaces of glomerular capillaries. Unique cell junctions, known as slit diaphragms, which feature nephrin and Neph family proteins in addition to components of adherens, tight, and gap junctions, connect adjacent podocyte foot processes. Single gene disorders affecting the slit diaphragm result in nephrotic syndrome in humans, characterized by massive loss of protein across the capillary wall. In addition to specialized cell junctions, interconnecting podocytes also adhere to the glomerular basement membrane (GBM) of the capillary wall. The GBM is a dense network of secreted, extracellular matrix (ECM) components and contains tissue-restricted isoforms of collagen IV and laminin in addition to other structural proteins and ECM regulators such as proteases and growth factors. The specialized niche of the GBM provides a scaffold for endothelial cells and podocytes to support their unique functions and human genetic mutations in GBM components lead to renal failure, thus highlighting the importance of cell-matrix interactions in the glomerulus. Cells adhere to ECM via adhesion receptors, including integrins, syndecans, and dystroglycan and in particular the integrin heterodimer α3β1 is required to maintain barrier integrity. Therefore, the sophisticated function of glomerular filtration relies on podocyte adhesion both at cell junctions and at the interface with the ECM. In health, the podocyte coordinates signals from cell junctions and cell-matrix interactions, in response to environmental cues in order to regulate filtration and as our understanding of mechanisms that control cell adhesion in the glomerulus develops, then insight into the effects of disease will improve. The ultimate goal will be to develop targeted therapies to prevent or repair defects in the filtration barrier and to restore glomerular function.

No MeSH data available.


Related in: MedlinePlus

Molecular components of the podocyte cell–matirx interface. Podocytes adhere to the underlying GBM using transmembrane adhesion receptors. The laminin-binding integrin α3β1 and the associated tetraspannin CD151 are highly expressed on the podocyte cell surface, in addition to adhesion receptors for other ECM ligands. Adhesion complexes form when activated integrins recruit adaptor, scaffold, and signaling proteins to their cytoplasmic tails. Integrins link to the actin cytoskeleton via two major axes; talin, vinculin, paxillin and integrin-linked kinase (ILK), PINCH, parvin. Podocytes attach to an ECM network containing laminin-521 networks, collagen IV α3α4α5 networks, agrin, perlecan, and nidogen.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4196579&req=5

Figure 3: Molecular components of the podocyte cell–matirx interface. Podocytes adhere to the underlying GBM using transmembrane adhesion receptors. The laminin-binding integrin α3β1 and the associated tetraspannin CD151 are highly expressed on the podocyte cell surface, in addition to adhesion receptors for other ECM ligands. Adhesion complexes form when activated integrins recruit adaptor, scaffold, and signaling proteins to their cytoplasmic tails. Integrins link to the actin cytoskeleton via two major axes; talin, vinculin, paxillin and integrin-linked kinase (ILK), PINCH, parvin. Podocytes attach to an ECM network containing laminin-521 networks, collagen IV α3α4α5 networks, agrin, perlecan, and nidogen.

Mentions: In order to adhere to the GBM, podocytes and endothelial cells utilize transmembrane adhesion receptors and the cell–matrix adhesion of podocytes was recently reviewed elsewhere (45). Adhesion receptors contain extracellular domains, which can bind to specific ECM proteins and intracellular domains that recruit effector proteins and link adhesion receptors to the cell cytoskeleton (Figure 3). A major family of proteins responsible for cell–ECM adhesion is the integrins.


The importance of podocyte adhesion for a healthy glomerulus.

Lennon R, Randles MJ, Humphries MJ - Front Endocrinol (Lausanne) (2014)

Molecular components of the podocyte cell–matirx interface. Podocytes adhere to the underlying GBM using transmembrane adhesion receptors. The laminin-binding integrin α3β1 and the associated tetraspannin CD151 are highly expressed on the podocyte cell surface, in addition to adhesion receptors for other ECM ligands. Adhesion complexes form when activated integrins recruit adaptor, scaffold, and signaling proteins to their cytoplasmic tails. Integrins link to the actin cytoskeleton via two major axes; talin, vinculin, paxillin and integrin-linked kinase (ILK), PINCH, parvin. Podocytes attach to an ECM network containing laminin-521 networks, collagen IV α3α4α5 networks, agrin, perlecan, and nidogen.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196579&req=5

Figure 3: Molecular components of the podocyte cell–matirx interface. Podocytes adhere to the underlying GBM using transmembrane adhesion receptors. The laminin-binding integrin α3β1 and the associated tetraspannin CD151 are highly expressed on the podocyte cell surface, in addition to adhesion receptors for other ECM ligands. Adhesion complexes form when activated integrins recruit adaptor, scaffold, and signaling proteins to their cytoplasmic tails. Integrins link to the actin cytoskeleton via two major axes; talin, vinculin, paxillin and integrin-linked kinase (ILK), PINCH, parvin. Podocytes attach to an ECM network containing laminin-521 networks, collagen IV α3α4α5 networks, agrin, perlecan, and nidogen.
Mentions: In order to adhere to the GBM, podocytes and endothelial cells utilize transmembrane adhesion receptors and the cell–matrix adhesion of podocytes was recently reviewed elsewhere (45). Adhesion receptors contain extracellular domains, which can bind to specific ECM proteins and intracellular domains that recruit effector proteins and link adhesion receptors to the cell cytoskeleton (Figure 3). A major family of proteins responsible for cell–ECM adhesion is the integrins.

Bottom Line: The GBM is a dense network of secreted, extracellular matrix (ECM) components and contains tissue-restricted isoforms of collagen IV and laminin in addition to other structural proteins and ECM regulators such as proteases and growth factors.The specialized niche of the GBM provides a scaffold for endothelial cells and podocytes to support their unique functions and human genetic mutations in GBM components lead to renal failure, thus highlighting the importance of cell-matrix interactions in the glomerulus.Cells adhere to ECM via adhesion receptors, including integrins, syndecans, and dystroglycan and in particular the integrin heterodimer α3β1 is required to maintain barrier integrity.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester , Manchester , UK ; Institute of Human Development, Faculty of Medical and Human Sciences, The University of Manchester , Manchester , UK ; Department of Paediatric Nephrology, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust , Manchester , UK.

ABSTRACT
Podocytes are specialized epithelial cells that cover the outer surfaces of glomerular capillaries. Unique cell junctions, known as slit diaphragms, which feature nephrin and Neph family proteins in addition to components of adherens, tight, and gap junctions, connect adjacent podocyte foot processes. Single gene disorders affecting the slit diaphragm result in nephrotic syndrome in humans, characterized by massive loss of protein across the capillary wall. In addition to specialized cell junctions, interconnecting podocytes also adhere to the glomerular basement membrane (GBM) of the capillary wall. The GBM is a dense network of secreted, extracellular matrix (ECM) components and contains tissue-restricted isoforms of collagen IV and laminin in addition to other structural proteins and ECM regulators such as proteases and growth factors. The specialized niche of the GBM provides a scaffold for endothelial cells and podocytes to support their unique functions and human genetic mutations in GBM components lead to renal failure, thus highlighting the importance of cell-matrix interactions in the glomerulus. Cells adhere to ECM via adhesion receptors, including integrins, syndecans, and dystroglycan and in particular the integrin heterodimer α3β1 is required to maintain barrier integrity. Therefore, the sophisticated function of glomerular filtration relies on podocyte adhesion both at cell junctions and at the interface with the ECM. In health, the podocyte coordinates signals from cell junctions and cell-matrix interactions, in response to environmental cues in order to regulate filtration and as our understanding of mechanisms that control cell adhesion in the glomerulus develops, then insight into the effects of disease will improve. The ultimate goal will be to develop targeted therapies to prevent or repair defects in the filtration barrier and to restore glomerular function.

No MeSH data available.


Related in: MedlinePlus