Morphologic determinant of tight junctions revealed by claudin-3 structures

Nakamura, Shun; Irie, Keiko; Tanaka, Hiroo; Nishikawa, Kyoji; Suzuki, Hiroshi; Saitoh, Yasunori; Tamura, Atsushi; Tsukita, Sachiko; Fujiyoshi, Yoshinori

doi:10.1038/s41467-019-08760-7

Cited by 64 publications

(105 citation statements)

References 51 publications

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“…Tight junctions are cell adhesion apparatuses that act as barriers and/or channels in the spaces between adjacent epithelial cells [40]. The expression of tight junction protein in the intestinal tract is age-speci c. For example, claudin is normally expressed in the human fetal small intestine, but not in the adult colon under homeostatic conditions [41].…”

Section: Discussionmentioning

confidence: 99%

Single-blinded Study Highlighting the Differences between the Small Intestines of Neonatal and Weaned Piglets

Chen

Jin

Shah

et al. 2020

Preprint

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Background: The gut is the body’s major immune structure, and the gut mucosa, which contains intraepithelial lymphocytes (IELs) and subepithelial natural immune cells, is considered the primary site for eliciting local immune responses to foreign antigens. Pigs are susceptible to intestinal infections at all life stages; however, neonates tend to be the most susceptible. This study compared the small intestine of neonatal and weaned piglets to provide a theoretical basis for preventing intestinal infectious diseases in neonatal piglets. Results: Histological analyses of weaned piglet intestines showed increased crypt depth, higher IEL count, and larger ileal Peyer’s patches compared with those of neonates. Additionally, the ileal villi of weaned piglets were longer than those of neonatal piglets. The expression of claudin-3 and occludin protein was remarkably higher in weaned piglets than in neonatal piglets. The numbers of CD3 + T cells, goblet cells, and secretory cells were also higher in the small intestine of weaned piglets than in those of neonates. The number of secretory IgA-positive cells in the jejunum was not significantly different between neonatal and weaned piglets. The gene expression of 12 pattern recognition receptors (PRRs), such as TLR1–10, MDA5, and RIG-I in the small intestines of both neonatal and weaned piglets was also examined. The mRNA expression of most pattern recognition receptors genes in the duodenum and jejunum was higher in weaners than in neonates; however, the inverse was true in the ileum. Compared with that in weaned piglets, there were significantly fewer CD3 + , CD4 + , and CD8 + T cells from peripheral blood-mononuclear cells in neonatal piglets. Conclusions: In this study, the physical and immunological components of small intestines of neonatal and weaned piglets were investigated. Our results provide preliminary data on differences in the immune mechanisms between the small intestines of 0- and 21-day-old piglets. Future studies could focus on additional developmental stages of pigs and how the differences in their small intestines affect the animal’s response to pathogens

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Section: Discussionmentioning

confidence: 99%

Single-blinded Study Highlighting the Differences between the Small Intestines of Neonatal and Weaned Piglets

Chen

Jin

Shah

et al. 2020

Preprint

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“…While the recent wealth of structural information on TARP/TARP-like complexes (Twomey et al, 2016, 2017a,b, 2018; Zhao et al, 2016, 2019; Chen et al, 2017; Herguedas et al, 2019) and claudins (Suzuki et al, 2014; Saitoh et al, 2015; Nakamura et al, 2019) has provided new insights into potential modulatory interfaces, the exact interactions are in fact ambiguous. The loops are often only visible at low thresholds in cryo-EM density maps, indicating that the loops are conformationally heterogeneous in the states that have been captured in structural studies and are not tightly bound.…”

Section: Discussionmentioning

confidence: 99%

“…3 C). TARPs have a claudin-like fold (Suzuki et al, 2014; Saitoh et al, 2015; Nakamura et al, 2019); their TMDs are a helical bundle composed of four helices (Fig. 3, D and E), and their ECD comprises a β-sheet, where variable size loops between β-strands extend toward the AMPAR LBDs.…”

Section: Architecture Of Ampars and Ampar–tarp Complexesmentioning

confidence: 99%

“…4, C and D). Interestingly, claudins, which share the overall fold with TARPs and GSG1L, also display variability in this structural element, with claudins 3, 4, and 19 lacking the ECH and claudin 15 having it present (Suzuki et al, 2014; Saitoh et al, 2015; Nakamura et al, 2019). It is possible that the lack of ECH in claudins 3, 4, and 19 could be due to crystal packing.…”

Section: Structural Conservation and Variability Among Regulatory Subunitsmentioning

confidence: 99%

“…An important distinction between claudins and claudin-fold AMPAR auxiliary subunits is various degrees of TM3 helix bending. While TARPs and GSG1L have a straight α-helical TM3, it bends in claudins, and the extent of bending defines the type of claudin–claudin interactions and affects the morphology and adhesiveness of the tight junctions (Suzuki et al, 2014; Saitoh et al, 2015; Nakamura et al, 2019).…”

Section: Structural Conservation and Variability Among Regulatory Subunitsmentioning

confidence: 99%

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Structural and functional insights into transmembrane AMPA receptor regulatory protein complexes

Twomey

Yelshanskaya

Sobolevsky

2019

Journal of General Physiology

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Fast excitatory neurotransmission is mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptor (AMPAR). AMPARs initiate depolarization of the postsynaptic neuron by allowing cations to enter through their ion channel pores in response to binding of the neurotransmitter glutamate. AMPAR function is dramatically affected by auxiliary subunits, which are regulatory proteins that form various complexes with AMPARs throughout the brain. The most well-studied auxiliary subunits are the transmembrane AMPAR regulatory proteins (TARPs), which alter the assembly, trafficking, localization, kinetics, and pharmacology of AMPARs. Recent structural and functional studies of TARPs and the TARP-fold germ cell-specific gene 1-like (GSG1L) subunit have provided important glimpses into how auxiliary subunits regulate the function of synaptic complexes. In this review, we put these recent structures in the context of new functional findings in order to gain insight into the determinants of AMPAR regulation by TARPs. We thus reveal why TARPs display a broad range of effects despite their conserved modular architecture.

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Synthetic Peptides with Genetic‐Codon‐Tailored Affinity for Assembling Tetraspanin CD81 at Cell Interfaces and Inhibiting Cancer Metastasis

Xu,

Gao,

et al. 2024

Angewandte Chemie

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Probing biomolecular interactions at cellular interfaces is crucial for understanding and interfering with life processes. Although affinity binders with site specificity for membrane proteins are unparalleled molecular tools, a high demand remains for novel multi‐functional ligands. In this study, a synthetic peptide (APQQ) with tight and specific binding to the untargeted extracellular loop of CD81 evolved from a genetically encoded peptide pool. With tailored affinity, APQQ flexibly accesses, site‐specifically binds, and forms a complex with CD81, enabling in‐situ tracking of the dynamics and activity of this protein in living cells, which has rarely been explored because of the lack of ligands. Furthermore, APQQ triggers the relocalization of CD81 from diffuse to densely clustered at cell junctions and modulates the interplay of membrane proteins at cellular interfaces. Motivated by these, efficient suppression of cancer cell migration, and inhibition of breast cancer metastasis were achieved in vivo.

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Morphologic determinant of tight junctions revealed by claudin-3 structures

Cited by 64 publications

References 51 publications

Single-blinded Study Highlighting the Differences between the Small Intestines of Neonatal and Weaned Piglets

Single-blinded Study Highlighting the Differences between the Small Intestines of Neonatal and Weaned Piglets

Structural and functional insights into transmembrane AMPA receptor regulatory protein complexes

Synthetic Peptides with Genetic‐Codon‐Tailored Affinity for Assembling Tetraspanin CD81 at Cell Interfaces and Inhibiting Cancer Metastasis

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