The role of claudins in homeostasis

A short guide to the tight junction

“…The characteristic TJ strands seen by FFEM are composed of claudin polymers, which are both key components of the barrier and constitute the pore pathway ( Fig. 2B ) ( Tsukita et al, 2019 ; Otani and Furuse, 2020 ; Piontek et al, 2020 ; Meoli and Günzel, 2023 ). Structural models and molecular dynamics simulations suggest that claudins polymerize in cis to form two parallel rows, which interact in trans with similar polymers on an adjacent cell ( Fig.…”

“…The simple classification of claudins as either barrier-forming or channel-forming can be further complicated, considering that interactions between different claudin isoforms suggest that they should be clustered into several distinct groups ( Tsukita et al, 2019 ; Piontek et al, 2020 ; Meoli and Günzel, 2023 ). For example, some claudins segregate into separate regions of the strand network, some claudins that cannot form homotypic strands can integrate into a network formed by a different claudin, and some claudins can disrupt a homotypic network formed by another claudin ( Gonschior et al, 2022 ; Shashikanth et al, 2022 ).…”

“…In general, multiple claudins are expressed within each cell type, and expression patterns are regulated spatially, temporally, and in response to developmental and pathological stimuli. Furthermore, within certain tissues, such as the intestine and kidney, the complement of expressed claudin proteins changes spatially, for example as a function of either differentiation along the crypt–villus axis or along the nephron segments, respectively ( Kiuchi-Saishin et al, 2002 ; Holmes et al, 2006 ; Yu, 2015 ; Meoli and Günzel, 2023 ). There appears to be significant functional redundancy within the claudin family as, in many cases, knockout (KO) of an individual claudin isoform does not lead to abnormal permeability in cultured cell models or mice ( Tokuda et al, 2014 ).…”

“…The onset of gallstones is promoted by KO of claudin-2 and claudin-3. Furthermore, many metabolic disorder pathologies in the kidneys are identified following KO of claudin-2, claudin-8, claudin-10a and claudin-16 ( Meoli and Günzel, 2023 ).…”

Molecular Dynamics Simulations of Claudin-10a and -10b Ion Channels: With Similar Architecture, Different Pore Linings Determine the Opposite Charge Selectivity

“…The members of the claudin family of tetraspan membrane proteins ( Figure S1 ) form the backbone of TJ strands. They constitute both barriers as well as channels that directly regulate paracellular permeability [ 3 , 4 , 5 , 6 ]. Functionally, claudins can be roughly grouped into (i) barrier-forming claudins (such as CLDN1, -3, -5, and -11) that almost completely block solute permeation, (ii) channel-forming claudins (such as CLDN2, -10a, -10b, -15, and -17) that form size- and charge-selective channels, and (iii) context-dependent claudins (such as CLDN4, -7, -8, and -16), whose permeability properties strongly depend on additional TJ components and conditions [ 1 ].…”