scholarly journals Extracellular chloride signals collagen IV network assembly during basement membrane formation

2016 ◽  
Vol 213 (4) ◽  
pp. 479-494 ◽  
Author(s):  
Christopher F. Cummings ◽  
Vadim Pedchenko ◽  
Kyle L. Brown ◽  
Selene Colon ◽  
Mohamed Rafi ◽  
...  
Keyword(s):  
Cell Culture ◽  
Basement Membrane ◽  
Collagen Iv ◽  
Atomic Level ◽  
Basement Membranes ◽  
Tissue Architecture ◽  
Dynamic Interactions ◽  
Conformational Switch ◽  
And Function ◽  
Fundamental Mechanism

Basement membranes are defining features of the cellular microenvironment; however, little is known regarding their assembly outside cells. We report that extracellular Cl− ions signal the assembly of collagen IV networks outside cells by triggering a conformational switch within collagen IV noncollagenous 1 (NC1) domains. Depletion of Cl− in cell culture perturbed collagen IV networks, disrupted matrix architecture, and repositioned basement membrane proteins. Phylogenetic evidence indicates this conformational switch is a fundamental mechanism of collagen IV network assembly throughout Metazoa. Using recombinant triple helical protomers, we prove that NC1 domains direct both protomer and network assembly and show in Drosophila that NC1 architecture is critical for incorporation into basement membranes. These discoveries provide an atomic-level understanding of the dynamic interactions between extracellular Cl− and collagen IV assembly outside cells, a critical step in the assembly and organization of basement membranes that enable tissue architecture and function. Moreover, this provides a mechanistic framework for understanding the molecular pathobiology of NC1 domains.

scholarly journals Peroxidasin-mediated bromine enrichment of basement membranes

2020 ◽  
Vol 117 (27) ◽  
pp. 15827-15836
Author(s):  
Cuiwen He ◽  
Wenxin Song ◽  
Thomas A. Weston ◽  
Caitlyn Tran ◽  
Ira Kurtz ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Knockout Mice ◽  
Structural Integrity ◽  
Secondary Ion Mass Spectrometry ◽  
Human Kidney ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Basement Membrane Protein ◽  
Mammalian Tissues ◽  
Cross Links

Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural integrity of basement membranes. The formation of sulfilimine cross-links depends on the ability of peroxidasin to use bromide and hydrogen peroxide substrates to produce hypobromous acid (HOBr). Once a sulfilimine cross-link is created, bromide is released into the extracellular space and becomes available for reutilization. Whether the HOBr generated by peroxidasin is used very selectively for creating sulfilimine cross-links or whether it also causes oxidative damage to bystander molecules (e.g., generating bromotyrosine residues in basement membrane proteins) is unclear. To examine this issue, we used nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to define the distribution of bromine in mammalian tissues. We observed striking enrichment of bromine (79Br,81Br) in basement membranes of normal human and mouse kidneys. In peroxidasin knockout mice, bromine enrichment of basement membranes of kidneys was reduced by ∼85%. Proteomic studies revealed bromination of tyrosine-1485 in the NC1 domain of α2 collagen IV from kidneys of wild-type mice; the same tyrosine was brominated in collagen IV from human kidney. Bromination of tyrosine-1485 was reduced by >90% in kidneys of peroxidasin knockout mice. Thus, in addition to promoting sulfilimine cross-links in collagen IV, peroxidasin can also brominate a bystander tyrosine. Also, the fact that bromine enrichment is largely confined to basement membranes implies that peroxidasin activity is largely restricted to basement membranes in mammalian tissues.

scholarly journals Kinesin-3 and kinesin-1 motors direct basement membrane protein secretion to a basal sub-region of the basolateral plasma membrane in epithelial cells

2021 ◽  
Author(s):  
Allison L. Zajac ◽  
Sally Horne-Badovinac
Keyword(s):  
Basement Membrane ◽  
Protein Secretion ◽  
Basolateral Membrane ◽  
Basement Membranes ◽  
Follicular Epithelium ◽  
List Type ◽  
Secretory Vesicles ◽  
Tissue Architecture ◽  
Basal Surface ◽  
Basement Membrane Protein

SUMMARYBasement membranes (BMs) are sheet-like extracellular matrices that line the basal surfaces of all epithelia. Since BM proteins form networks, they likely need to be secreted near the basal surface. However, the location of their secretion site and how it is selected are unknown. Working in the Drosophila follicular epithelium, we identified two kinesins essential for normal BM formation. Our data suggest the two kinesins work together to transport Rab10+ BM protein-filled secretory vesicles towards the basal surface along the polarized microtubule array common to epithelia. This kinesin transport biases BM protein secretion basally. When kinesins are depleted, BM proteins are mis-secreted to more apical regions of the lateral membrane, creating ectopic BM protein networks between cells that disrupt cell movements and tissue architecture. These results introduce a new transport step in the BM protein secretion pathway and highlight the importance of controlling the sub-cellular exocytic site of network-forming proteins.HighlightsA kinesin-3 and a kinesin-1 are required for normal basement membrane (BM) assemblyKinesins move Rab10+ BM secretory vesicles basally on polarized microtubule arraysTransport biases BM exocytosis to basal subregions of the basolateral membraneLoss of kinesins creates ectopic BM networks that disrupt tissue architecture

Altered synthesis of laminin 1 and absence of basement membrane component deposition in (beta)1 integrin-deficient embryoid bodies

2000 ◽  
Vol 113 (2) ◽  
pp. 259-268 ◽  
Author(s):  
M. Aumailley ◽  
M. Pesch ◽  
L. Tunggal ◽  
F. Gaill ◽  
R. Fassler
Keyword(s):  
Basement Membrane ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Mouse Genetics ◽  
Embryoid Bodies ◽  
Membrane Formation ◽  
Beta 1 Integrin ◽  
Laminin 1

Basement membranes are the earliest extracellular matrices produced during embryogenesis. They result from synthesis and assembly into a defined supramolecular architecture of several components, including laminins, collagen IV, nidogen, and proteoglycans. In vitro studies have allowed us to propose an assembly model based on the polymerisation of laminin and collagen IV in two separate networks associated together by nidogen. How nucleation of polymers and insolubilisation of the different components into a basement membrane proceed in vivo is, however, unknown. A most important property of several basement membrane components is to provide signals controling the activity of adjacent cells. The transfer of information is mediated by interactions with cell surface receptors, among them integrins. Mouse genetics has demonstrated that the absence of these interactions is not compatible with development as deletion of either laminin (gamma)1 chain or integrin (beta)1 chain lead to lethality of mouse embryos at the peri-implantation stage. We have used embyoid bodies as a model system recapitulating the early steps of embryogenesis to unravel the respective roles of laminin and (beta)1 integrins in basement membrane formation. Our data show that there is formation of a basal lamina in wild-type, but not in (beta)1-integrin deficient, embryoid bodies. Surprisingly, in the absence of (beta)1 integrins, laminin 1 was not secreted in the extracellular space due to a rapid switch off of laminin (alpha)1 chain synthesis which normally drives the secretion of laminin heterotrimers. These results indicate that (beta)1 integrins are required for the initiation of basement membrane formation, presumably by applying a feed-back regulation on the expression of laminin (alpha)1 chain and other components of basement membranes.

Vocal Cord Basement Membrane in Non-Sudden Infant Death Syndrome Cases

1999 ◽  
Vol 2 (5) ◽  
pp. 440-445 ◽  
Author(s):  
Eumênia C.C. Castro ◽  
L. Cesar Peres
Keyword(s):  
Basement Membrane ◽  
Vocal Cord ◽  
Sudden Infant Death Syndrome ◽  
Infant Death ◽  
Periodic Acid ◽  
Sudden Infant Death ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Sudden Infant ◽  
Periodic Acid Schiff

Vocal cord basement membrane thickening (VCBMT) has been observed in children with sudden infant death syndrome (SIDS). It has been proposed that this lesion could be used as a positive indicator of this syndrome in autopsies of children who have died unexpectedly. The present investigation aimed to analyze vocal cord basement membranes from autopsies of children 0 to 365 days old. A total of 134 larynges were analyzed. Histological sections of paraffin-embedded larynges stained with H&E and submitted to histochemical staining with periodic acid–Schiff (PAS), Masson's trichrome, syrius red, and Carstairs were used for light microscopy analysis. Immunohistochemistry with monoclonal anti-collagen IV antibody was used to determine the nature of VCBMT. The study was completed with morphometry of H&E–and PAS-stained sections and revision of the clinical information contained in the hospital files. VCBMT was found in 25 cases (18.7%) and showed characteristics of normal basement membrane, including immunoreactivity to collagen IV. Our data support the conclusions that VCBMT is frequently seen in pediatric autopsies, is seen in children in all age-groups studied whose deaths were due to causes other than SIDS, and is commonly associated with infectious diseases. Like SIDS, VCBMT occurs in the first year of life.

The molecular basis of glomerular basement membrane disorders

2018 ◽  
Author(s):  
Rachel Lennon ◽  
Neil Turner
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Heparan Sulphate ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Glomerular Disease ◽  
The Body ◽  
Monogenic Disorders ◽  
Filtration Barrier

The glomerular basement membrane (GBM) is a condensed network of extracellular matrix molecules which provides a scaffold and niche to support the function of the overlying glomerular cells. Within the glomerulus, the GBM separates the fenestrated endothelial cells, which line capillary walls from the epithelial cells or podocytes, which cover the outer aspect of the capillaries. In common with basement membranes throughout the body, the GBM contains core components including collagen IV, laminins, nidogens, and heparan sulphate proteoglycans. However, specific isoforms of these proteins are required to maintain the integrity of the glomerular filtration barrier.Across the spectrum of glomerular disease there is alteration in glomerular extracellular matrix (ECM) and a number of histological patterns are recognized. The GBM can be thickened, expanded, split, and irregular; the mesangial matrix may be expanded and glomerulosclerosis represents a widespread accumulation of ECM proteins associated with loss of glomerular function. Whilst histological patterns may follow a sequence or provide diagnostic clues, there remains limited understanding about the mechanisms of ECM regulation and how this tight control is lost in glomerular disease. Monogenic disorders of the GBM including Alport and Pierson syndromes have highlighted the importance of both collagen IV and laminin isoforms and these observations provide important insights into mechanisms of glomerular disease.

scholarly journals The Absence of Nidogen 1 Does Not Affect Murine Basement Membrane Formation

2000 ◽  
Vol 20 (18) ◽  
pp. 7007-7012 ◽  
Author(s):  
Monzur Murshed ◽  
Neil Smyth ◽  
Nicolai Miosge ◽  
Jörg Karolat ◽  
Thomas Krieg ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Embryonic Stem ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Null Mutation ◽  
Membrane Structures ◽  
Membrane Formation ◽  
Nidogen 1

ABSTRACT Nidogen 1 is a highly conserved protein in mammals,Drosophila melanogaster, Caenorhabditis elegans, and ascidians and is found in all basement membranes. It has been proposed that nidogen 1 connects the laminin and collagen IV networks, so stabilizing the basement membrane, and integrates other proteins, including perlecan, into the basement membrane. To define the role of nidogen 1 in basement membranes in vivo, we produced a null mutation of the NID-1 gene in embryonic stem cells and used these to derive mouse lines. Homozygous animals produce neither nidogen 1 mRNA nor protein. Surprisingly, they show no overt abnormalities and are fertile, their basement membrane structures appearing normal. Nidogen 2 staining is increased in certain basement membranes, where it is normally only found in scant amounts. This occurs by either redistribution from other extracellular matrices or unmasking of nidogen 2 epitopes, as its production does not appear to be upregulated. The results show that nidogen 1 is not required for basement membrane formation or maintenance.

Protein Substrate Alters Cell Physiology in Primary Culture of Vocal Fold Epithelial Cells

2021 ◽  
pp. 1-14
Author(s):  
Emily E. Kimball ◽  
Lea Sayce ◽  
Xiaochuan C. Xu ◽  
Chase M. Kruszka ◽  
Bernard Rousseau
Keyword(s):  
Cell Culture ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Vocal Fold ◽  
Phase Contrast ◽  
Mesenchymal Cell ◽  
Mesenchymal Cells ◽  
Collagen Iv ◽  
Collagen I ◽  
Protein Substrate

The basement membrane interacts directly with the vocal fold epithelium. Signaling between the basement membrane and the epithelium modulates gene regulation, differentiation, and proliferation. The purpose of this study was to identify an appropriate simple single-protein substrate for growth of rabbit vocal fold epithelial cells. Vocal folds from 3 New Zealand white rabbits (<i>Oryctolagus cuniculus</i>) were treated to isolate epithelial cells, and cells were seeded onto cell culture inserts coated with collagen I, collagen IV, laminin, or fibronectin. Transepithelial electrical resistance (TEER) was measured, and phase contrast microscopy, PanCK, CK14, and E-cadherin immunofluorescence were utilized to assess for epithelial cell-type characteristics. Further investigation via immunofluorescence labeling was conducted to assess proliferation (Ki67) and differentiation (Vimentin). There was a significant main effect of substrate on TEER, with collagen IV eliciting the highest, and laminin the lowest resistance. Assessment of relative TEER across cell lines identified a larger range of TEER in collagen I and laminin. Phase contrast imaging identified altered morphology in the laminin condition, but cell layer depth did not appear to be related to TEER, differentiation, or morphology. Ki67 staining additionally showed no significant difference in proliferation. All conditions had confluent epithelial cells and dispersed mesenchymal cells, with increased mesenchymal cell numbers over time; however, a higher proportion of mesenchymal cells was observed in the laminin condition. The results suggest collagen IV is a preferable basement membrane substrate for in vitro vocal fold epithelial primary cell culture, providing consistent TEER and characteristic cell morphology, and that laminin is an unsuitable substrate for vocal fold epithelial cells and may promote mesenchymal cell proliferation.

scholarly journals The incubation of laminin, collagen IV, and heparan sulfate proteoglycan at 35 degrees C yields basement membrane-like structures.

1989 ◽  
Vol 108 (4) ◽  
pp. 1567-1574 ◽  
Author(s):  
D S Grant ◽  
C P Leblond ◽  
H K Kleinman ◽  
S Inoue ◽  
J R Hassell
Keyword(s):  
Basement Membrane ◽  
Heparan Sulfate ◽  
Three Dimensional ◽  
Collagen Iv ◽  
Heparan Sulfate Proteoglycan ◽  
Basement Membranes ◽  
Sulfate Proteoglycan ◽  
Lamina Densa ◽  
Dimensional Network ◽  
Type C

Three basement membrane components, laminin, collagen IV, and heparan sulfate proteoglycan, were mixed and incubated at 35 degrees C for 1 h, during which a precipitate formed. Centrifugation yielded a pellet which was fixed in either potassium permanganate for ultrastructural studies, or in formaldehyde for Lowicryl embedding and immunolabeling with protein A-gold or anti-rabbit immunoglobulin-gold. Three types of structures were observed and called types A, B, and C. Type B consisted of 30-50-nm-wide strips that were dispersed or associated into a honeycomb-like pattern, but showed no similarity with basement membranes. Immunolabeling revealed that type B strips only contained heparan sulfate proteoglycan. The structure was attributed to self-assembly of this proteoglycan. Type A consisted of irregular strands of material that usually accumulated into semisolid groups. Like basement membrane, the strands contained laminin, collagen IV, and heparan sulfate proteoglycan, and, at high magnification, they appeared as a three-dimensional network of cord-like elements whose thickness averaged approximately 3 nm. But, unlike the neatly layered basement membranes, the type A strands were arranged in a random, disorderly manner. Type C structures were convoluted sheets composed of a uniform, dense, central layer which exhibited a few extensions on both surfaces and was similar in appearance and thickness to the lamina densa of basement membranes. Immunolabeling showed that laminin, collagen IV, and proteoglycan were colocalized in the type C sheets. At high magnification, the sheets appeared as a three-dimensional network of cords averaging approximately 3 nm. Hence, the organization, composition, and ultrastructure of type C sheets made them similar to the lamina densa of authentic basement membranes.

Role of Lateral Interactions in Type IV Collagen Network Mechanics

2013 ◽  
Author(s):  
Lazarina Gyoneva ◽  
Mohammad F. Hadi ◽  
Yoav Segal ◽  
Kevin D. Dorfman ◽  
Victor H. Barocas
Keyword(s):  
Mechanical Properties ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Hereditary Disease ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Type I ◽  
Lateral Interactions ◽  
Type Iv

The basement membrane is a specialized part of the extra-cellular matrix. It is usually characterized as a scaffold for epithelial cells but in some tissues it serves other, mechanical, roles [1]. The mechanical properties of the basement membrane are mainly determined by one of its main constituents — type IV collagen. Unlike the well-known fibrous type I collagen, collagen IV assembles into planar networks (Fig. 1) [2]. The α 1(IV) and α 2(IV) collagen IV chains assemble into the so-called major chain network, present in all basement membranes. The α 3(IV), α 4(IV), α 5(IV) collagen IV chains form the minor chain network which is found only in the adult basement membranes of the kidney glomerular capillaries (GBM), ocular lens (LBM), cochlea, and the testes [3]. The minor chains have a higher number of cysteine residues, allowing them to form a higher number of lateral interactions. In the minor chain network, the greater potential to interact laterally manifests in the formation of super-coils, which are rarely observed in the major chain network [4]. Increasing the number of cross-links in a polymeric material is known to increase material stiffness; therefore, it is believed that the minor chain network confers basement membranes with additional strength and stability [5]. In the hereditary disease Alport syndrome, a mutation causes the absence of the minor chain network. The GBM and LBM of Alport patients appear weakened and unable to meet their mechanical demands, further supporting this theory [6]. The objective of this study was to evaluate the importance of cross-linking in the minor chains for the mechanical properties of type IV collagen networks, specifically in the GBM and LBM where the absence of the minor chains has an observed mechanical effect.

Site-specific cleavage of basement membrane collagen IV during Drosophila metamorphosis

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 1061-1069 ◽  
Author(s):  
L.I. Fessler ◽  
M.L. Condic ◽  
R.E. Nelson ◽  
J.H. Fessler ◽  
J.W. Fristrom
Keyword(s):  
Drosophila Melanogaster ◽  
Amino Acid ◽  
Basement Membrane ◽  
Collagen Iv ◽  
Basement Membranes ◽  
The Other ◽  
Supramolecular Network ◽  
Site Specific ◽  
Basement Membrane Collagen ◽  
Membrane Collagen

Breakdown of basement membranes is an important step in the controlled rearrangement of cells during metamorphosis, cell migration, and metastatic spread of tumor cells. One of our two laboratories found a unique collagenous peptide that only appears during metamorphosis of Drosophila melanogaster. The other laboratory previously reported that during 20-hydroxyecdysone-induced eversion of Drosophila imaginal discs a glycoprotein named gp125 arises (Birr et al., 1990). We show that these two peptides are identical and that they are formed from basement membrane collagen IV. Cleavage occurs at an imperfection of this homotrimeric collagen helix between residues 755/756 in the sequence CALDE/IKMPAK. The peptide is the carboxyl fragment, 100,647 M(r), as derived from the amino acid sequence of the collagen alpha 1(IV) chain. The corresponding amino fragment was also recovered from a disulfide-linked aggregate. This specific cleavage supports the concept of highly targeted, controlled breakdown of basement membranes during metamorphosis. Furthermore, these cuts occur at strategic sites of the predicted supramolecular network of collagen IV molecules of Drosophila basement membranes.

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