The Claudin Megatrachea Protein Complex

Jaspers, Martin H. J.; Nolde, Kai; Behr, Matthias; Joo, Seolhee; Plessmann, Uwe; Nikolov, Miroslav; Urlaub, Henning; Schuh, Reinhard

doi:10.1074/jbc.m112.399410

Cited by 29 publications

(25 citation statements)

References 50 publications

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“…In Drosophilia megatrachea, the invertebrate homolog of claudin was also shown to associate with Sec61β. 30) Importantly, the r values (Materials and Methods: Immunoprecipitation) were found to be less than 0.05 in all cases. Further, extraction with Triton X-100 rather than NP-40 resulted in weaker claudin-4 (r<0.01) and claudin-1 (r=0.019) association with Sec61β (Fig.…”

Section: Claudin-4 Association With Sec61βmentioning

confidence: 89%

Sec61β Regulates Barrier Functions of Tight Junction through Expression of Claudin-4 in Madin–Darby Canine Kidney Cells

Washiyama

Koizumi

Fujii

et al. 2014

Biological & Pharmaceutical Bulletin

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Sec61β is the β subunit of the Sec61 translocon and is responsible for expression and delivery of basolateral membrane proteins, including claudins, major constituents of tight junction (TJ). In the present study, the effect of Sec61β overexpression on TJ barrier functions in Madin-Darby canine kidney (MDCK) cells were investigated by monitoring transepithelial electrical resistance (TER) and the expression and distribution of claudins. We adopted the time required by TER to reach 50% (T 1/2 ) as a measure of TJ modulation rate. Sec61β overexpression increased TER by post-transcriptionally upregulating claudin-4 expression and resulted in increased TER. Sec61β overexpression increased TJ modulation rates (lower T 1/2 ), in conjunction with enhanced delivery of claudin-4 from and to plasma membranes. Marked co-distribution and indirect association of claudin-4 with Sec61β were observed, contributing to the enhanced delivery of claudin-4. Thus, Sec61β may be a novel TJ modulation target, including barrier function and modulation rates for drug delivery systems.

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Section: Claudin-4 Association With Sec61βmentioning

confidence: 89%

Sec61β Regulates Barrier Functions of Tight Junction through Expression of Claudin-4 in Madin–Darby Canine Kidney Cells

Washiyama

Koizumi

Fujii

et al. 2014

Biological & Pharmaceutical Bulletin

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“…This notion is further substantiated by the recent mass spectrometrybased identification of Mcr along with several membrane-associated SJ proteins as components of the Claudin complex (Jaspers et al, 2012). However, earlier work had shown that Mcr is secreted by S2 cells into the culture medium (Stroschein-Stevenson et al, 2006).…”

Section: Mcr Is Essential For Epithelial Barrier Functionmentioning

confidence: 91%

“…Furthermore, it is not known how the diverse functions of SJs are integrated and modulated in different tissues and under different physiological conditions. Recent genetic and proteomic studies suggest that many SJ-associated proteins remain to be identified (Hijazi et al, 2009;Nilton et al, 2010;Tiklová et al, 2010;Syed et al, 2011;Ile et al, 2012;Jaspers et al, 2012;Bonnay et al, 2013). We identified Macroglobulin complement-related (Mcr) as a new SJ-associated protein.…”

Section: Introductionmentioning

confidence: 99%

The transmembrane protein Macroglobulin complement-related is essential for septate junction formation and epithelial barrier function inDrosophila

2014

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Occluding cell-cell junctions in epithelia form physical barriers that separate different membrane domains, restrict paracellular diffusion and prevent pathogens from spreading across tissues. In invertebrates, these functions are provided by septate junctions (SJs), the functional equivalent of vertebrate tight junctions. How the diverse functions of SJs are integrated and modulated in a multiprotein complex is not clear, and many SJ components are still unknown. Here we report the identification of Macroglobulin complement-related (Mcr), a member of the conserved α-2-macroglobulin (α2M) complement protein family, as a novel SJ-associated protein in Drosophila. Whereas α2M complement proteins are generally known as secreted factors that bind to surfaces of pathogens and target them for phagocytic uptake, Mcr represents an unusual α2M protein with a predicted transmembrane domain. We show that Mcr protein localizes to lateral membranes of epithelial cells, where its distribution overlaps with SJs. Several SJ components are required for the correct localization of Mcr. Conversely, Mcr is required in a cellautonomous fashion for the correct membrane localization of SJ components, indicating that membrane-bound rather than secreted Mcr isoforms are involved in SJ formation. Finally, we show that loss of Mcr function leads to morphological, ultrastructural and epithelial barrier defects resembling mutants lacking SJ components. Our results, along with previous findings on the role of Mcr in phagocytosis, suggest that Mcr plays dual roles in epithelial barrier formation and innate immunity. Thus, Mcr represents a novel paradigm for investigating functional links between occluding junction formation and pathogen defense mechanisms.

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“…Claudin-like proteins have been found in C. elegans (Asano et al, 2003, Simske, 2013, Simske and Hardin, 2011 and Drosophila (Jaspers et al, 2012), where they form part of a different type of intercellular junction. The C. elegans claudin-like proteins (CLC-1 to CLC-5) localize to or near septate junctions and appear to play a role in cell adhesion and epithelial permeability via the paracellular pathway (Asano et al, 2003).…”

mentioning

confidence: 99%

“…The C. elegans claudin-like proteins (CLC-1 to CLC-5) localize to or near septate junctions and appear to play a role in cell adhesion and epithelial permeability via the paracellular pathway (Asano et al, 2003). Drosophila homologues of claudins, Megatrachea, Sinuous and Kune-Kune, localize to the septate junctions (invertebrate homologue of the tight junctions), and their loss results in the disruption of junctional structure, epithelial adhesion and permeability (Behr et al, 2003, Jaspers et al, 2012, Nelson et al, 2010, Wu et al, 2004. Therefore, even though the sequences of the non-chordate invertebrate and vertebrate claudins are highly divergent (Simske, 2013), the non-vertebrate claudin-like proteins appear to play similar roles to their vertebrate counterparts, albeit within different junctional complexes.…”

mentioning

confidence: 99%

Evolution of the vertebrate claudin gene family: insights from a basal vertebrate, the sea lamprey

Mukendi

Dean²,

Lala³

et al. 2016

Int. J. Dev. Biol.

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Claudins are major constituents of tight junctions, contributing both to their intercellular sealing and selective permeability properties. While claudins and claudin-like molecules are present in some invertebrates, the association of claudins with tight junctions has been conclusively documented only in vertebrates. Here we report the sequencing, phylogenetic analysis and comprehensive spatiotemporal expression analysis of the entire claudin gene family in the basal extant vertebrate, the sea lamprey. Our results demonstrate that clear orthologues to about half of all mammalian claudins are present in the lamprey, suggesting that at least one round of whole genome duplication contributed to the diversification of this gene family. Expression analysis revealed that claudins are expressed in discrete and specific domains, many of which represent vertebratespecific innovations, such as in cranial ectodermal placodes and the neural crest; whereas others represent structures characteristic of chordates, e.g. pronephros, notochord, somites, endostyle and pharyngeal arches. By comparing the embryonic expression of claudins in the lamprey to that of other vertebrates, we found that ancestral expression patterns were often preserved in higher vertebrates. Morpholino mediated loss of Cldn3b demonstrated a functional role for this protein in placode and pharyngeal arch morphogenesis. Taken together, our data provide novel insights into the origins and evolution of the claudin gene family and the significance of claudin proteins in the evolution of vertebrates.

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The Claudin Megatrachea Protein Complex

Cited by 29 publications

References 50 publications

Sec61β Regulates Barrier Functions of Tight Junction through Expression of Claudin-4 in Madin–Darby Canine Kidney Cells

Sec61β Regulates Barrier Functions of Tight Junction through Expression of Claudin-4 in Madin–Darby Canine Kidney Cells

The transmembrane protein Macroglobulin complement-related is essential for septate junction formation and epithelial barrier function inDrosophila

Evolution of the vertebrate claudin gene family: insights from a basal vertebrate, the sea lamprey

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