Transmembrane collagen XVII is a novel component of the glomerular filtration barrier

Hurskainen, Tiina; Moilanen, Jyri; Sormunen, Raija; Franzke, Claus‐Werner; Soininen, Raija; Loeffek, S.; Huilaja, Laura; Nuutinen, Matti; Bruckner‐Tuderman, Leena; Autio–Harmainen, Helena; Tasanen, Kaisa

doi:10.1007/s00441-012-1368-x

Cited by 33 publications

(31 citation statements)

References 32 publications

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“…There is a recent report showing that the collagen XVII is a component of the podocyte filtration barrier in the kidney glomerular basement membrane [60]. A possible involvement of this transmembrane collagen in the embryonic blood-CSF barrier remains to be studied).…”

Section: Resultsmentioning

confidence: 98%

Mechanisms That Determine the Internal Environment of the Developing Brain: A Transcriptomic, Functional and Ultrastructural Approach

Liddelow

Dzięgielewska

et al. 2013

PLoS ONE

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We provide comprehensive identification of embryonic (E15) and adult rat lateral ventricular choroid plexus transcriptome, with focus on junction-associated proteins, ionic influx transporters and channels. Additionally, these data are related to new structural and previously published permeability studies. Results reveal that most genes associated with intercellular junctions are expressed at similar levels at both ages. In total, 32 molecules known to be associated with brain barrier interfaces were identified. Nine claudins showed unaltered expression, while two claudins (6 and 8) were expressed at higher levels in the embryo. Expression levels for most cytoplasmic/regulatory adaptors (10 of 12) were similar at the two ages. A few junctional genes displayed lower expression in embryos, including 5 claudins, occludin and one junctional adhesion molecule. Three gap junction genes were enriched in the embryo. The functional effectiveness of these junctions was assessed using blood-delivered water-soluble tracers at both the light and electron microscopic level: embryo and adult junctions halted movement of both 286Da and 3kDa molecules into the cerebrospinal fluid (CSF). The molecular identities of many ion channel and transporter genes previously reported as important for CSF formation and secretion in the adult were demonstrated in the embryonic choroid plexus (and validated with immunohistochemistry of protein products), but with some major age-related differences in expression. In addition, a large number of previously unidentified ion channel and transporter genes were identified for the first time in plexus epithelium. These results, in addition to data obtained from electron microscopical and physiological permeability experiments in immature brains, indicate that exchange between blood and CSF is mainly transcellular, as well-formed tight junctions restrict movement of small water-soluble molecules from early in development. These data strongly indicate the brain develops within a well-protected internal environment and the exchange between the blood, brain and CSF is transcellular and not through incomplete barriers.

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Section: Resultsmentioning

confidence: 98%

Mechanisms That Determine the Internal Environment of the Developing Brain: A Transcriptomic, Functional and Ultrastructural Approach

Liddelow

Dzięgielewska

et al. 2013

PLoS ONE

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“…Human diseases and mouse models have demonstrated that loss of ColXVII expression is associated with rudimentary poorly developed HDs and separation of the epidermis from the basement membrane upon mechanical friction [12], [18], [19]. Here we assessed the adhesive strength of murine Col17a1 − / − keratinocytes using two different in vitro detachment assays.…”

Section: Resultsmentioning

confidence: 99%

“…The generation of the Col17a1 − / − mice has been described elsewhere [12]. Briefly, the targeting vector contained 6.7 kb genomic DNA with arms of 4.3 kb and 2.4 kb.…”

Section: Methodsmentioning

confidence: 99%

Transmembrane Collagen XVII Modulates Integrin Dependent Keratinocyte Migration via PI3K/Rac1 Signaling

et al. 2014

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The hemidesmosomal transmembrane component collagen XVII (ColXVII) plays an important role in the anchorage of the epidermis to the underlying basement membrane. However, this adhesion protein seems to be also involved in the regulation of keratinocyte migration, since its expression in these cells is strongly elevated during reepithelialization of acute wounds and in the invasive front of squamous cell carcinoma, while its absence in ColXVII-deficient keratinocytes leads to altered cell motility. Using a genetic model of murine Col17a1− /− keratinocytes we elucidated ColXVII mediated signaling pathways in cell adhesion and migration. Col17a1− /− keratinocytes exhibited increased spreading on laminin 332 and accelerated, but less directed cell motility. These effects were accompanied by increased expression of the integrin subunits β4 and β1. The migratory phenotype, as evidenced by formation of multiple unstable lamellipodia, was associated with enhanced phosphoinositide 3-kinase (PI3K) activity. Dissection of the signaling pathway uncovered enhanced phosphorylation of the β4 integrin subunit and the focal adhesion kinase (FAK) as activators of PI3K. This resulted in elevated Rac1 activity as a downstream consequence. These results provide mechanistic evidence that ColXVII coordinates keratinocyte adhesion and directed motility by interfering integrin dependent PI3K activation and by stabilizing lamellipodia at the leading edge of reepithelializing wounds and in invasive squamous cell carcinoma.

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“…2). Immunoelectron microscopy has revealed that collagen XVII is localized in foot processes of podocytes and in the glomerular BM (Hurskainen et al 2012). Collagen XVII exists as a full-length transmembrane protein and a soluble 120-kDa ectodomain that is proteolytically released from the cell surface by the sheddases of a disintegrin and metalloproteinase (ADAM) family, ADAM-10, −9 and −17 (Franzke et al 2009).…”

Section: Localized and Intermediate Subtypes Of Junctional Ebmentioning

confidence: 99%

“…Animal models Col17-knockout mice demonstrate skin blisters and display postnatal foot process effacement and glomerular BM splitting (Nishie et al 2007;Hurskainen et al 2012). Nevertheless, no functional studies with regard to glomerular filtration are available and no renal anomalies have been detected in patients with junctional EB lacking collagen XVII.…”

Section: Localized and Intermediate Subtypes Of Junctional Ebmentioning

confidence: 99%

Renal-skin syndromes

Has

2017

Cell Tissue Res

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Renal-skin syndroms are a group of genetic disorders with renal and cutaneous manifestations that target molecular components present in both organs. Inherited renal-skin syndromes are mainly associated with defects of cell-matrix adhesion. We provide a non-exhaustive overview of the main molecular players at cell-matrix adhesions in mouse models and in human genetic disorders affecting kidney and skin. Renal and urinary tract involvement is described in all four major epidermolysis bullosa types and, in particular, in junctional subtypes and in recessive dystrophic epidermolysis bullosa. Here, we describe in detail those subtypes for which reno-urinary involvement is a constant and primary feature. Furthermore, complex multiorgan disorders with a predisposition to malignancies or attributable to metabolic defects that involve both kidney and skin are briefly summarized.

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Transmembrane collagen XVII is a novel component of the glomerular filtration barrier

Cited by 33 publications

References 32 publications

Mechanisms That Determine the Internal Environment of the Developing Brain: A Transcriptomic, Functional and Ultrastructural Approach

Mechanisms That Determine the Internal Environment of the Developing Brain: A Transcriptomic, Functional and Ultrastructural Approach

Transmembrane Collagen XVII Modulates Integrin Dependent Keratinocyte Migration via PI3K/Rac1 Signaling

Renal-skin syndromes

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