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The kidney tight junction (Review).

Hou J - Int. J. Mol. Med. (2014)

Bottom Line: The tight junction is an important subcellular organelle which plays a vital role in epithelial barrier function.Claudin, as the integral membrane component of tight junctions, creates a paracellular transport pathway for various ions to be reabsorbed by the kidneys.Defects in claudin function can cause a wide spectrum of kidney diseases, such as hypomagnesemia, hypercalciuria, kidney stones and hypertension.

View Article: PubMed Central - PubMed

Affiliation: Washington University Renal Division, St. Louis, MO 63110, USA.

ABSTRACT
The tight junction is an important subcellular organelle which plays a vital role in epithelial barrier function. Claudin, as the integral membrane component of tight junctions, creates a paracellular transport pathway for various ions to be reabsorbed by the kidneys. This review summarizes advances in claudin structure, function and pathophysiology in kidney diseases. Different claudin species confer selective paracellular permeability to each of three major renal tubular segments: the proximal tubule, the thick ascending limb of Henle's loop and the distal nephron. Defects in claudin function can cause a wide spectrum of kidney diseases, such as hypomagnesemia, hypercalciuria, kidney stones and hypertension. Studies using transgenic mouse models with claudin mutations have recapitulated several of these renal disease phenotypes and have elucidated the underlying biological mechanisms. Modern recording approaches based upon scanning ion conductance microscopy may resolve the biophysical nature of claudin transport function and provide novel insight into tight junction architecture.

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Related in: MedlinePlus

Claudin topology. The schematic cartoon illustrates the conserved regions in a claudin molecule. The first extracellular loop (ECL1) is important for paracellular ion selectivity and hepatitis C virus (HCV) binding; the second extracellular loop is important for claudin trans-interaction and Clostridium perfringens enterotoxin (CPE) binding. The YV motif in the carboxyl terminus is important for zonula occludens (ZO)-1 binding. TMD1–4, transmembrane domains 1 to 4. Modified from a previous study (14).
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f1-ijmm-34-06-1451: Claudin topology. The schematic cartoon illustrates the conserved regions in a claudin molecule. The first extracellular loop (ECL1) is important for paracellular ion selectivity and hepatitis C virus (HCV) binding; the second extracellular loop is important for claudin trans-interaction and Clostridium perfringens enterotoxin (CPE) binding. The YV motif in the carboxyl terminus is important for zonula occludens (ZO)-1 binding. TMD1–4, transmembrane domains 1 to 4. Modified from a previous study (14).

Mentions: Claudins are tetraspan proteins consisting of a family of at least 26 members (13) ranging in molecular mass from 20–28 kDa. Claudins have four transmembrane domains, two extracellular loops, amino- and carboxy-terminal cytoplasmic domains and a short cytoplasmic turn (14) (Fig. 1). The first extracellular loop (ECL1) of claudin consists of ~50 amino acids with a common motif (-GLWCC; PROSITE ID: PS01346) (15), and intercalating negative (16,17) and positive (18,19) charges that contribute to paracellular ion selectivity. The GLWCC motif is critical as a receptor for hepatitis C viral entry (20). The charges in ECL1 regulate paracellular ion selectivity through electrostatic effects (21). The second extracellular loop (ECL2) consists of ~25 amino acids with a predicted helix-turn-helix motif that mediates trans-claudin interactions (22) and claudin interactions with the Clostridium perfringens enterotoxin (23). The carboxy-terminal domain of claudin contains a post-synaptic density 95/discs large/zonula occludens-1 (PDZ) binding domain (YV) that is critical for interactions with the submembrane scaffold protein, zonula occludens (ZO)-1 and correct localization in the tight junction (24).


The kidney tight junction (Review).

Hou J - Int. J. Mol. Med. (2014)

Claudin topology. The schematic cartoon illustrates the conserved regions in a claudin molecule. The first extracellular loop (ECL1) is important for paracellular ion selectivity and hepatitis C virus (HCV) binding; the second extracellular loop is important for claudin trans-interaction and Clostridium perfringens enterotoxin (CPE) binding. The YV motif in the carboxyl terminus is important for zonula occludens (ZO)-1 binding. TMD1–4, transmembrane domains 1 to 4. Modified from a previous study (14).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214347&req=5

f1-ijmm-34-06-1451: Claudin topology. The schematic cartoon illustrates the conserved regions in a claudin molecule. The first extracellular loop (ECL1) is important for paracellular ion selectivity and hepatitis C virus (HCV) binding; the second extracellular loop is important for claudin trans-interaction and Clostridium perfringens enterotoxin (CPE) binding. The YV motif in the carboxyl terminus is important for zonula occludens (ZO)-1 binding. TMD1–4, transmembrane domains 1 to 4. Modified from a previous study (14).
Mentions: Claudins are tetraspan proteins consisting of a family of at least 26 members (13) ranging in molecular mass from 20–28 kDa. Claudins have four transmembrane domains, two extracellular loops, amino- and carboxy-terminal cytoplasmic domains and a short cytoplasmic turn (14) (Fig. 1). The first extracellular loop (ECL1) of claudin consists of ~50 amino acids with a common motif (-GLWCC; PROSITE ID: PS01346) (15), and intercalating negative (16,17) and positive (18,19) charges that contribute to paracellular ion selectivity. The GLWCC motif is critical as a receptor for hepatitis C viral entry (20). The charges in ECL1 regulate paracellular ion selectivity through electrostatic effects (21). The second extracellular loop (ECL2) consists of ~25 amino acids with a predicted helix-turn-helix motif that mediates trans-claudin interactions (22) and claudin interactions with the Clostridium perfringens enterotoxin (23). The carboxy-terminal domain of claudin contains a post-synaptic density 95/discs large/zonula occludens-1 (PDZ) binding domain (YV) that is critical for interactions with the submembrane scaffold protein, zonula occludens (ZO)-1 and correct localization in the tight junction (24).

Bottom Line: The tight junction is an important subcellular organelle which plays a vital role in epithelial barrier function.Claudin, as the integral membrane component of tight junctions, creates a paracellular transport pathway for various ions to be reabsorbed by the kidneys.Defects in claudin function can cause a wide spectrum of kidney diseases, such as hypomagnesemia, hypercalciuria, kidney stones and hypertension.

View Article: PubMed Central - PubMed

Affiliation: Washington University Renal Division, St. Louis, MO 63110, USA.

ABSTRACT
The tight junction is an important subcellular organelle which plays a vital role in epithelial barrier function. Claudin, as the integral membrane component of tight junctions, creates a paracellular transport pathway for various ions to be reabsorbed by the kidneys. This review summarizes advances in claudin structure, function and pathophysiology in kidney diseases. Different claudin species confer selective paracellular permeability to each of three major renal tubular segments: the proximal tubule, the thick ascending limb of Henle's loop and the distal nephron. Defects in claudin function can cause a wide spectrum of kidney diseases, such as hypomagnesemia, hypercalciuria, kidney stones and hypertension. Studies using transgenic mouse models with claudin mutations have recapitulated several of these renal disease phenotypes and have elucidated the underlying biological mechanisms. Modern recording approaches based upon scanning ion conductance microscopy may resolve the biophysical nature of claudin transport function and provide novel insight into tight junction architecture.

Show MeSH
Related in: MedlinePlus