Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several isoforms of the gap junction protein connexin (Cx) have been identified in a variety of tissues that communicate intercellular signals between adjacent cells. In the kidney, Cx37, Cx40, and Cx43 are localized in the vasculature, glomerulus, and tubular segments in a punctuate pattern, typical of classic gap junction channels. We performed immunohistochemistry in the mouse, rat, and rabbit kidney to study the localization of Cx30 protein, a new member of the Cx family. The vasculature, glomerulus, and proximal nephron segments were devoid of staining in all three species. Unexpectedly, Cx30 was found throughout the luminal membrane of select cells in the distal nephron. Expression of Cx30 was highest in the rat, which also showed some diffuse cytosolic labeling, continuous from the medullary thick ascending limb to the collecting duct system, and with the highest level in the distal convoluted tubule. Labeling in the mouse and rabbit was much less, limited to intercalated cells in the connecting segment and cortical collecting duct, where the apical signal was particularly strong. A high-salt-containing diet and culture medium upregulated Cx30 expression in the rat inner medulla and in M1 cells, respectively. The distinct, continuous labeling of the luminal plasma membrane and upregulation by high salt suggest that Cx30 may function as a hemichannel involved in the regulation of salt reabsorption in the distal nephron.
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PMID:Localization of connexin 30 in the luminal membrane of cells in the distal nephron. 1607 80

Several isoforms of connexin (Cx) proteins have been identified in a variety of tissues where they play a role in intercellular communication, either as the components of gap junctions or as large, nonselective pores known as hemichannels. This investigation seeks to identify the localization and regulation of Cx30.3 in mouse, rat, and rabbit kidney using a Cx30.3(+/lacZ) transgenic approach and immunofluorescence. Cx30.3 was detected in all three species and predominantly in the renal medulla. Both the nuclear lacZ staining indicative of Cx30.3 expression and indirect immunohistochemistry provided the same results. Cx30.3 immunolabeling was mainly punctate in the mouse, typical for gap junctions. In contrast, it showed continuous apical plasma membrane localization in certain tubule segments in the rat and rabbit kidney, suggesting that it may also function as hemichannels. In the cortex, Cx30.3 was localized in the intercalated cells of the cortical collecting duct, because the immunoreactive cells did not label for AQP2, a marker for principal cells. In the medulla, dense Cx30.3 staining was confined to the ascending thin limbs of the loop of Henle, because the immunoreactive cells did not label for AQP1, a marker of the descending thin limbs. Immunoblotting studies indicated that Cx30.3 expression was unchanged in response to either high or low salt intake or in spontaneously hypertensive rats. Cx30.3 appears to be constitutively expressed in certain renal tubular segments and cells and its role in overall kidney function remains to be investigated.
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PMID:Connexin 30.3 is expressed in the kidney but not regulated by dietary salt or high blood pressure. 1864 92

Connexins are the main components of gap junction channels, which are important for intercellular communication. In the kidney, several members of the connexin (Cx) family have been identified. Renal vascular expression and hemodynamic impacts have so far been shown for Cx37, Cx40, and Cx43. Additionally, Cx30, Cx30.3, and Cx43 have been identified to be part of tubular epithelial gap junctions and/or hemichannels. However, the localization and role of other Cx family members in renal epithelial structures remain undetermined. We aimed to localize Cx37 in the kidney to obtain information on its epithelial expression and potential functions. Immunohistochemistry in rodent kidney showed characteristic punctate patterns in the vasculature and along the nephron. Strong basolateral expression was found in the thick ascending limb and distal convoluted tubule. Weaker abundances were found in the proximal tubule and the collecting duct also at the basolateral side. In situ hybridization and real-time PCR of isolated nephron segments confirmed this distribution at the mRNA level. Ultrastructurally, Cx37 immunostaining was confined to basolateral cell interdigitations and infoldings. As a functional approach, rats were fed low- or high-salt diets. Compared with control and high-salt diets, rats treated with low-salt diet showed significantly increased Cx37 mRNA and protein levels. This may be indicative of an adaptive tubular response to changes in sodium reabsorption. In summary, renal epithelia express Cx37 in their basolateral membranes. Here, the formation of Cx37 gap junctions may be involved in cellular communication and adjustments of vectorial epithelial transport.
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PMID:Connexin 37 is localized in renal epithelia and responds to changes in dietary salt intake. 1982 78

ATP in the renal tubular fluid is an important regulator of salt and water reabsorption via purinergic calcium signaling that involves the P2Y2 receptor, ENaC, and AQP2. Recently, we have shown that connexin (Cx) 30 hemichannels are localized to the non-junctional apical membrane of cells in the distal nephron-collecting duct (CD) and release ATP into the tubular fluid upon mechanical stimuli, leading to reduced salt and water reabsorption. Cx30(-/-) mice show salt-dependent elevations in BP and impaired pressure-natriuresis. Thus, we hypothesized that increased tubular flow rate leads to Cx30-dependent purinergic intracellular calcium ([Ca(2+)]i) signaling in the CD. Cortical CDs (CCDs) from wild type and Cx30(-/-) mice were freshly dissected and microperfused in vitro. Using confocal fluorescence imaging and the calcium-sensitive fluorophore pair Fluo-4 and Fura Red, we found that increasing tubular flow rate from 2 to 20 nl/min caused a significant 2.1-fold elevation in [Ca(2+)]i in wild type CCDs. This response was blunted in Cx30(-/-) CCDs ([Ca(2+)]i increased only 1.2-fold, p < 0.0001 vs. WT, n = 6 each). To further test our hypothesis we performed CD [Ca(2+)]i imaging in intact mouse kidneys in vivo using multiphoton microscopy and micropuncture delivery of the calcium-sensitive fluorophore Rhod-2. We found intrinsic, spontaneous [Ca(2+)]i oscillations in free-flowing CDs of wild type but not Cx30(-/-) mice. The [Ca(2+)]i oscillations were sensitive also to P2-receptor inhibition by suramin. Taken together, these data confirm that mechanosensitive Cx30 hemichannels mediate tubular ATP release and purinergic calcium signaling in the CD which mechanism plays an important role in the regulation of CD salt and water reabsorption.
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PMID:ATP releasing connexin 30 hemichannels mediate flow-induced calcium signaling in the collecting duct. 2413 32