Tight Junctional Localization of Claudin-16 Is Regulated by Syntaxin 8 in Renal Tubular Epithelial Cells

Ikari, Akira; Tonegawa, Chie; Sanada, Ayumi; Kimura, Tōru; Sakai, Hideki; Hayashi, Hideharu; Hasegawa, Hajime; Yamaguchi, Masahiko; Yamazaki, Yoji; Endo, Shunsuke; Matsunaga, Toshiyuki; Sugatani, Junko

doi:10.1074/jbc.m113.541193

Cited by 21 publications

(31 citation statements)

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“…1B). As described in a previous report using the same antibody (24), the majority of both signals were colocalized in the basolateral side of the TAL. Immunofluorescent staining of claudin-16 also did not show any apparent difference between LETO and OLETF rats throughout the experimental period (Fig.…”

Section: Resultsmentioning

confidence: 66%

Downregulation of transient receptor potential M6 channels as a cause of hypermagnesiuric hypomagnesemia in obese type 2 diabetic rats

Takayanagi

Shimizu

Tayama

et al. 2015

American Journal of Physiology-Renal Physiology

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We assessed the expression profile of Mg(2+)-transporting molecules in obese diabetic rats as a cause of hypermagnesiuric hypomagnesemia, which is involved in the development of insulin resistance, hypertension, and coronary diseases. Kidneys were obtained from male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) obese diabetic rats at the ages of 16, 24, and 34 wk. Expression profiles were studied by real-time PCR and immunohistochemistry together with measurements of urine Mg(2+) excretion. Urine Mg(2+) excretion was increased in 24-wk-old OLETF rats and hypomagnesemia was apparent in 34-wk-old OLETF rats but not in LETO rats (urine Mg(2+) excretion: 0.16 ± 0.01 μg·min(-1)·g body wt(-1) in 24-wk-old LETO rats and 0.28 ± 0.01 μg·min(-1)·g body wt(-1) in 24-wk-old OLETF rats). Gene expression of transient receptor potential (TRP)M6 was downregulated (85.5 ± 5.6% in 34-wk-old LETO rats and 63.0 ± 3.5% in 34-wk-old OLETF rats) concomitant with Na(+)-Cl(-) cotransporter downregulation, whereas the expression of claudin-16 in tight junctions of the thick ascending limb of Henle was not different. The results of the semiquantitative analysis of immunohistochemistry were consistent with these findings (TRPM6: 0.49 ± 0.04% in 16-wk-old LETO rats, 0.10 ± 0.01% in 16-wk-old OLETF rats, 0.52 ± 0.03% in 24-wk-old LETO rats, 0.10 ± 0.01% in 24-wk-old OLETF rats, 0.48 ± 0.02% in 34-wk-old LETO rats, and 0.12 ± 0.02% in 34-wk-old OLETF rats). Gene expression of fibrosis-related proinflammatory cytokines as well as histological changes showed that the hypermagnesiuria-related molecular changes and tubulointerstitial nephropathy developed independently. TRPM6, located principally in distal convoluted tubules, appears to be a susceptible molecule that causes hypermagnesiuric hypomagnesemia as a tubulointerstitial nephropathy-independent altered tubular function in diabetic nephropathy.

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Section: Resultsmentioning

confidence: 66%

Downregulation of transient receptor potential M6 channels as a cause of hypermagnesiuric hypomagnesemia in obese type 2 diabetic rats

Takayanagi

Shimizu

Tayama

et al. 2015

American Journal of Physiology-Renal Physiology

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“…TJ proteins accumulate in early endosomes as a first station after internalization. Several reports indicate that claudin‐1, claudin‐5, claudin‐16, occludin, JAM‐A, and ZO‐1 accumulate in early endosomes in both epithelial and endothelial cells . Their presence in early endosomes is closely associated with diminished barrier function (hyperpermeability) .…”

Section: Early Endosomes: a Center Of Sortingmentioning

confidence: 99%

“…ESCRT is known to be involved in the trafficking of transmembrane proteins to the lysosome, as well as other processes, including autophagy and TGN trafficking . In kidney epithelial cells, claudin‐16 recycling is dependent on Rab11 and STX8 …”

Section: Recycling Pathways For Tj Proteinsmentioning

confidence: 99%

“…Several reports indicate that claudin-1, claudin-5, claudin-16, occludin, JAM-A, and ZO-1 accumulate in early endosomes in both epithelial and endothelial cells. 23,25,32,40,48,[68][69][70][71] Their presence in early endosomes is closely associated with diminished barrier function (hyperpermeability). 32,40,47,71 Furthermore, Rab5A depletion using small interfering RNA (siRNA) increased claudin-1 association with the plasma membrane in the human endothelial cell line EA hy.926 and also stabilized brain endothelial barrier function owing to an inability to further process internalized junction proteins.…”

Section: Endocytic Trafficking and Sorting Of Tj Proteinsmentioning

confidence: 99%

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Endocytosis of tight junction proteins and the regulation of degradation and recycling

Stamatovic¹,

Johnson²,

Sladojević

et al. 2017

Annals of the New York Academy of Sciences

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Internalization of tight junction (TJ) proteins from the plasma membrane is a pivotal mechanism regulating TJ plasticity and function in both epithelial and endothelial barrier tissues. Once internalized, the TJ proteins enter complex vesicular machinery, where further trafficking is directly dependent on the initiating stimulus and downstream signaling pathways that regulate the sorting and destiny of TJ proteins, as well as on cell and barrier responses. The destiny of internalized TJ proteins is recycling to the plasma membrane or sorting to late endosomes and degradation. This review highlights recent advances in our knowledge of endocytosis and vesicular trafficking of TJ proteins in both epithelial and endothelial cells. A greater understanding of these processes may allow for the development of methods to modulate barrier permeability for drug delivery or preventing barrier dysfunction in disease states.

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“…In MDCK cells, low extracellular Mg ++ levels reduced the localization of claudin-16 to the tight junction, which can be abolished by the extracellular signal-regulated kinase (ERK) inhibitor – U0126 [33]. With yeast two-hybrid screening approach, Ikari and colleagues have demonstrated direction interaction between claudin-16 and syntaxin-8, an important protein trafficking regulator [34]. Knockdown of syntaxin-8 in renal cells decreased the cell surface localization of claudin-16.…”

Section: The Regulatory Mechanism Of the Paracellular Channel Made Ofmentioning

confidence: 99%

Claudins and mineral metabolism

Hou

2016

Current Opinion in Nephrology and Hypertension

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Purpose of review The tight junction (TJ) conductance made of the claudin based paracellular channel is important in the regulation of calcium and magnesium reabsorption in the kidney. This review describes recent findings of the structure, the function, and the physiologic regulation of claudin-14, claudin-16 and claudin-19 channels that through protein interactions confer calcium and magnesium permeability to the TJ. Recent findings Mutations in two TJ genes – claudin-16 and claudin-19 cause the inherited renal disorder – familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Recent genome-wide association study (GWAS) has identified claudin-14 as a major risk gene of hypercalciuric nephrolithiasis. Claudin-14 interacts with claudin-16 and inhibits its cation permselectivity. Transgenic overexpression of claudin-14 in the kidney generated the FHHNC-like phenotypes. The crystal structure of claudin-19 has recently been resolved allowing the reconstruction of a claudin assembly model from cis-dimers made of claudin-16 and claudin-19 interaction. MicroRNAs have been identified as novel regulators of the claudin-14 gene. The microRNA-claudin-14 operon is directly regulated by the Ca++ sensing receptor (CaSR) gene in response to hypercalcemia. Summary The paracellular pathway in the kidney is particularly important for mineral metabolism. Three claudin proteins – claudin-14, claudin-16 and claudin-19 contribute to the structure and function of this paracellular pathway. Genetic mutations and gene expression changes in these claudins may lead to alteration of the paracellular permeability to calcium and magnesium, ultimately affecting renal mineral metabolism. Claudins can be regulated on several levels including transcription, microRNA repression, trafficking, phosphorylation, and interaction.

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Tight Junctional Localization of Claudin-16 Is Regulated by Syntaxin 8 in Renal Tubular Epithelial Cells

Cited by 21 publications

References 48 publications

Downregulation of transient receptor potential M6 channels as a cause of hypermagnesiuric hypomagnesemia in obese type 2 diabetic rats

Downregulation of transient receptor potential M6 channels as a cause of hypermagnesiuric hypomagnesemia in obese type 2 diabetic rats

Endocytosis of tight junction proteins and the regulation of degradation and recycling

Claudins and mineral metabolism

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