Structure and function of claudins

Abstract

Claudins are tetraspan transmembrane proteins of tight junctions. They determine the barrier properties of this type of cell-cell contact existing between the plasma membranes of two neighbouring cells, such as occurring in endothelia or epithelia. Claudins can completely tighten the paracellular cleft for solutes, and they can form paracellular ion pores. It is assumed that the extracellular loops specify these claudin functions. It is hypothesised that the larger first extracellular loop is critical for determining the paracellular tightness and the selective ion permeability. The shorter second extracellular loop may cause narrowing of the paracellular cleft and have a holding function between the opposing cell membranes. Sequence analysis of claudins has led to differentiation into two groups, designated as classic claudins (1-10, 14, 15, 17, 19) and non-classic claudins (11-13, 16, 18, 20-24), according to their degree of sequence similarity. This is also reflected in the derived sequence-structure function relationships for extracellular loops 1 and 2. The concepts evolved from these findings and first tentative molecular models for homophilic interactions may explain the different functional contribution of the two extracellular loops at tight junctions.

Tight junction-based epithelial microenvironment and cell proliferation

“…Although the homotypic and/ or heterotypic interactions of claudin-1, -2, -3, -5, -6, -11, -14 and -19 in forming TJ strands have been examined in claudin-free L fibroblastic cells, more detailed studies are required to fully understand the critical molecular bases of TJ strands Morita et al, 2002;Krause et al, 2008). Among the family members, claudin-11 and -19 each appear to form TJ strands by themselves, based on both knockout mouse studies and cell culture studies (Gow et al, 1999;Miyamoto et al, 2005).…”

Inhibition of MicroRNA‐155 Supports Endothelial Tight Junction Integrity Following Oxygen‐Glucose Deprivation

“…Passive diffusion through the BBB is regulated by brain endothelial tight junctions (TJs), which are composed of transmembrane and cytosolic TJ‐associated protein complexes 1, 2. Among major TJ proteins, which play a critical role in the formation and integrity of vascular barrier are occludin, claudins (claudin‐5 [CLDN5] and claudin‐1 [CLDN1], among other family members), and a major scaffolding protein ZO‐1 (member of the zonula occludens protein family) 3, 4. Expression, cellular distribution, and interaction of these proteins with each other are critical for paracellular permeability and TJ‐mediated signaling 5.…”

Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na + and Mg 2+ transport

“…Usually, claudins are capable of homomeric and homotypic interactions; heteromeric and heterotypic interactions are less common and depend on the compatibility of the claudin partners (for a review, see ref. 1).…”