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Review
. 2016 Feb 5;15(2):339-59.
doi: 10.1021/acs.jproteome.5b00769. Epub 2016 Jan 12.

Systems Proteomics View of the Endogenous Human Claudin Protein Family

Fei Liu, Michael Koval  1 , Shoba Ranganathan, Susan Fanayan, William S Hancock  2 , Emma K Lundberg  3 , Ronald C Beavis  4 , Lydie Lane  5 , Paula Duek  5 , Leon McQuade, Neil L Kelleher  6 , Mark S Baker
Affiliations
Review

Systems Proteomics View of the Endogenous Human Claudin Protein Family

Fei Liu et al. J Proteome Res. .

Abstract

Claudins are the major transmembrane protein components of tight junctions in human endothelia and epithelia. Tissue-specific expression of claudin members suggests that this protein family is not only essential for sustaining the role of tight junctions in cell permeability control but also vital in organizing cell contact signaling by protein-protein interactions. How this protein family is collectively processed and regulated is key to understanding the role of junctional proteins in preserving cell identity and tissue integrity. The focus of this review is to first provide a brief overview of the functional context, on the basis of the extensive body of claudin biology research that has been thoroughly reviewed, for endogenous human claudin members and then ascertain existing and future proteomics techniques that may be applicable to systematically characterizing the chemical forms and interacting protein partners of this protein family in human. The ability to elucidate claudin-based signaling networks may provide new insight into cell development and differentiation programs that are crucial to tissue stability and manipulation.

Keywords: Membrane protein complexes; cell-contact signaling; chemical proteomics; membrane proteomics; systems proteomics; targeted proteomics; top-down proteomics.

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Figures

Figure 1
Figure 1
(a) General scheme of the claudin protein structure; (b) secondary structural motifs found in the ECL loops of the X-ray structure of mouse claudin-15.
Figure 2
Figure 2
Known or hypothetical PTMs of claudins and the regions in which they are predicted to occur. Predicted PTMs include phospohorylation (red oval), palmitoylation (yellow line), ubiquitination (blue circle), proteolysis (green marks), and glycosylation (gray box).
Figure 3
Figure 3
Top-down and bottom-up proteomics: advantages (in bold) and disadvantages (in gray).
Figure 4
Figure 4
Simplified scheme of the epithelial apical junctional complex, showing a subset of protein constituents, including tetraspan transmembrane proteins (claudins, occludin), single-pass transmembrane proteins (JAM-A, cadherin), cytosolic scaffold proteins (ZO-1, ZO-2, catenins), signaling proteins (RhoA, MLCK), and the actin cytoskeleton. The Crumbs/PALS/PATJ polarity complex is also shown, which defines the apical/basolateral axis and is directly associated with tight junctions via scaffold protein interactions.
Figure 5
Figure 5
Diagram of the protein interaction network of claudin-1. The diagram was made using Cytoscape. In orange are the intrinsic membrane proteins with at least one transmembrane domain. In yellow are the peripheral membrane proteins. These two groups contain plasma membrane proteins and endomembrane system proteins (endosome, endoplasmic reticulum, Golgi apparatus, and cytoplasmic vesicles). Membrane proteins from mitochondria or nucleus are not included in these two groups. In green are cytosolic, nuclear, and mitochondrial proteins. In blue are secreted proteins (with a signal peptide and no transmembrane domains). The pink border indicates proteins found in tight junctions. Red edges connect CLDN1 (diamond) with its direct interacting partners: TJP1/ZO-1, TJP2/ZO-2, TJP3/ZO-3, MPDZ, INADL, TACSTD2, SRC, KRT76, LNX1, CD81, CD9, OCLN, MARVELD2, MARVELD3, CLDN3, CLDN7, MMP14, MMP2, and EFNB1 (rectangles). Interactions with non-human proteins are not included in the network but briefly described in the text.
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