ZFIN ID: ZDB-PUB-130211-14
The tight junction protein claudin-b regulates epithelial permeability and sodium handling in larval zebrafish, Danio rerio
Kwong, R.W., and Perry, S.F.
Date: 2013
Source: Am. J. Physiol. Regul. Integr. Comp. Physiol. 304(7): R504--513 (Journal)
Registered Authors:
Keywords: Claudin-b, epithelial permeability, sodium, tight junction proteins, zebrafish
MeSH Terms: Animals; Chlorides/metabolism; Claudins/genetics; Claudins/metabolism*; Embryo, Nonmammalian/metabolism (all 18) expand
PubMed: 23364531 Full text @ Am. J. Physiol. Regul. Integr. Comp. Physiol.
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The functional role of the tight junction protein claudin-b in larval zebrafish (Danio rerio) was investigated. We showed that claudin-b protein is expressed at epithelial cell-cell contacts on the skin. Translational gene knockdown of claudin-b protein expression caused developmental defects, including edema in the pericardial cavity and yolk sac. Claudin-b morphants exhibited an increase in epithelial permeability to the paracellular marker polyethylene glycol (PEG-4000) and fluorescein isothiocyanate-dextran (FD-4). Accumulation of FD-4 was confined mainly to the yolk sac and pericardial cavity in the claudin-b morphants, suggesting these regions became particularly leaky in the absence of claudin-b expression. Additionally, Na+ efflux was substantially increased in the claudin-b morphants which contributed to a significant reduction in whole-body Na+ levels. These results indicate that claudin-b normally acts as a paracellular barrier to Na+. Nevertheless, the elevated loss of Na+ in the morphants was compensated by an increase in Na+ uptake. Notably, we observed that the increased Na+ uptake in the morphants was attenuated in the presence of the selective Na+/Cl--cotransporter (NCC) inhibitor metolazone, or during exposure to Cl--free water. These results suggested that the increased Na+ uptake in the morphants was at least in part mediated by NCC. Furthermore, treatment with an H+-ATPase inhibitor bafilomycin A1 was found to reduce Na+ uptake in the morphants, suggesting that H+-ATPase activity was essential to provide a driving force for Na+ uptake. Overall, the results suggest that claudin-b plays an important role in regulating epithelial permeability and Na+ handling in zebrafish.