CLDN8 gene

The CLDN8 gene (CLDN8 stands for Claudin-8) is a protein-coding gene located on chromosome 21q22.11. An important paralog of this gene is CLDN17. The CLDN8 gene codes for claudin-8 (see claudins below).

This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junctions (TJ). Tight junctions serve as a physical barrier to prevent the free passage of solutes and water through the paracellular space between epithelial and endothelial cell layers. They also play a crucial role in maintaining cell polarity and signal transduction. The protein encoded by CLDN8, claudin-8, plays an important role in the paracellular cation barrier of the distal renal tubule and in the paracellular barrier to prevent sodium reflux in the distal colon.

Differential expression of the CLDN8 gene has been observed in colorectal carcinomas and renal cell tumors. Claudin-8 and, together with claudin-7, is an immunohistochemical marker for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma. Associated signaling pathways include blood-brain barrier and immune cell transmigration, VCAM-1/CD106 signaling and cell-cell junction organization.

Diseases associated with CLDN8 include renal oncocytoma and oncocytoma .

The paracellular passage of ions and small molecules through epithelia is controlled by tight junctions , which consist of complex networks of claudin polymers that form tight protein seals between neighboring cells. How this mechanism enables the paracellular passage of specific ions or small molecules without compromising the barrier function is still unknown.

Remarkably, only a subset of claudins can assemble into characteristic homotypic networks, whereas tight junctions formed by multiple claudins exhibit nanoscale organizational principles of intermixing, integration, induction, segregation and exclusion of strand assemblies. So-called channel-forming claudins are spatially separated from barrier-forming claudins by determinants that are mainly encoded in their extracellular domains.

The protein claudin-8 can combine with other claudins to regulate the structural and functional strand dynamics of tight junctions. The protein can assemble with clausin-4 (CLDN4) to form tight junction strands that contain anion-selective channels that mediate, for example, paracellular chloride permeability in the collecting tubules of the kidney.

1. Gonschior H et al. (2022) Nanoscale segregation of channel and barrier claudins enables paracellular ion flux. Nat Commun 13:4985).
2. Hempel C et al. (2020) Assembly of Tight Junction Strands: Claudin-10b and Claudin-3 Form Homo-Tetrameric Building Blocks that Polymerize in a Channel-Independent Manner. J Mol Biol 432:2405-2427.
3. Piontek J et al. (2020) Molecular architecture and assembly of the tight junction backbone. Biochim Biophys Acta Biomembr 1862:183279.
4. Shashikanth N et al. (2022) Tight junction channel regulation by interclaudin interference. Nat Commun13:3780.