Boron is a vital micronutrient in plants and may be essential for animal growth and development. Whereas the role of boron in the life cycle of plants is well documented, nothing is known about boron homeostasis and function in animal cells. NaBC1, the mammalian homolog of AtBor1, is a borate transporter. In the absence of borate, NaBC1 conducts Na(+) and OH(-) (H(+)), while in the presence of borate, NaBC1 functions as an electrogenic, voltage-regulated, Na(+)-coupled B(OH)(4)(-) transporter. At low concentrations, borate activated the MAPK pathway to stimulate cell growth and proliferation, and at high concentrations, it was toxic. Accordingly, overexpression of NaBC1 shifted both effects of borate to the left, whereas knockdown of NaBC1 halted cell growth and proliferation. These findings may reveal a previously unrecognized role for NaBC1 in borate homeostasis and open the way to better understanding of the many presumed physiological roles of borate in animals.

The SLC26 transporters are a family of mostly luminal Cl− and HCO3 − transporters. The transport mechanism and the Cl−/HCO3 − stoichiometry are not known for any member of the family. To address these questions, we simultaneously measured the HCO3 − and Cl− fluxes and the current or membrane potential of slc26a3 and slc26a6 expressed in Xenopus laevis oocytes and the current of the transporters expressed in human embryonic kidney 293 cells. slc26a3 mediates a coupled 2Cl−/1HCO3 − exchanger. The membrane potential modulated the apparent affinity for extracellular Cl− of Cl−/HCO3 − exchange by slc26a3. Interestingly, the replacement of Cl− with NO3 − or SCN− uncoupled the transport, with large NO3 − and SCN− currents and low HCO3 − transport. An apparent uncoupled current was also developed during the incubation of slc26a3-expressing oocytes in HCO3 −-buffered Cl−-free media. These findings were used to develop a turnover cycle for Cl− and HCO3 − transport by slc26a3. Cl− and HCO3 − flux measurements revealed that slc26a6 mediates a 1Cl−/2HCO3 − exchange. Accordingly, holding the membrane potential at 40 and −100 mV accelerated and inhibited, respectively, Cl−-mediated HCO3 − influx, and holding the membrane potential at −100 mV increased HCO3 −-mediated Cl− influx. These findings indicate that slc26a6 functions as a coupled 1Cl−/2HCO3 − exchanger. The significance of isoform-specific Cl− and HCO3 − transport stoichiometry by slc26a3 and slc26a6 is discussed in the context of diseases of epithelial Cl− absorption and HCO3 − secretion.

3 ؊ transport. Stimulation of CFTR with forskolin markedly inhibited NBC3 activity. This inhibition was prevented by the inhibition of protein kinase A. NBC3 and CFTR could be reciprocally coimmunoprecipitated from transfected HEK cells and from the native pancreas and submandibular and parotid glands. Precipitation of NBC3 or CFTR from transfected HEK293 cells and from the pancreas and submandibular gland also coimmunoprecipitated EBP50. Glutathione S-transferase-EBP50 pulled down CFTR and hNBC3 from cell lysates when expressed individually and as a complex when expressed together. Notably, the deletion of the C-terminal PDZ binding motifs of CFTR or hNBC3 prevented coimmunoprecipitation of the proteins and inhibition of hNBC3 activity by CFTR. We conclude that CFTR and NBC3 reside in the same HCO 3 ؊ -transporting complex with the aid of PDZ domain-containing scaffolds, and this interaction is essential for regulation of NBC3 activity by CFTR. Furthermore, these findings add additional evidence for the suggestion that CFTR regulates the overall trans-cellular HCO 3 ؊ transport by regulating the activity of all luminal HCO 3 ؊ secretion and salvage mechanisms of secretory epithelial cells. HCO 3Ϫ concentration is tightly controlled in all biological fluids including fluids secreted by exocrine glands. The ductal systems or their equivalents are the sites of active regulation of HCO 3 Ϫ content of the secreted fluids. This is also the site of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) 1 (1-5). The transporters participating in ductal HCO 3 Ϫ homeostasis and their regulation are only partially known. Probably, the best results are available in the salivary glands and pancreatic ducts. Active regulation of luminal HCO 3 Ϫ concentration and pH i requires the regulation of both HCO 3 Ϫ secretory and absorptive mechanisms. HCO 3 Ϫ secretion is believed to occur by HCO 3 Ϫ influx across the basolateral membrane mediated by a Na ϩ -HCO 3 Ϫ cotransport mechanism (6, 7). The transporter mediating this activity is probably pNBC1, the pancreatic isoform of the electrogenic Na ϩ -HCO 3 Ϫ cotransporter family (8, 9). HCO 3 Ϫ efflux across the luminal membrane (LM) requires the activity of a Cl Ϫ /HCO 3 Ϫ exchange mechanism (6, 10, 11) and is dependent on the expression of CFTR both in human and in animal models (11,12).In the resting state, secretory glands have to absorb HCO 3 Ϫ . The transporters involved in HCO 3 Ϫ absorption are only beginning to emerge. HCO 3 Ϫ influx across the LM is in part the result of Na ϩ /H ϩ exchange mediated by NHE3 (13,14). However, in recent studies with the pancreatic (13) and the submandibular gland (SMG) ducts (9), we showed that Ͼ50% HCO 3 Ϫ absorption (H ϩ secretion) is mediated by more than one Na ϩ -dependent mechanism that is different from any known NHE isoform. Furthermore, we found that the SMG duct and acinar cells express several splice variants of NBC3 (rat orthologues NBCn1B-D) and used anti-NBC3 antibodies to localize the proteins to the LM (...

No abstract

Background: Slc26a2 is an SO 4 2Ϫ transporter, mutations in which cause diastrophic dysplasia. How Slc26a2 transports SO 4

Background: Slc26a2 is a SO 4 2Ϫ transporter that is mutated in diastrophic dysplasia. The role of Slc26a2 in several chondrocyte functions is unknown. Results: Slc26a2 is activated by IGF-1 to regulate chondrocyte, proliferation, differentiation, proteoglycan synthesis, and size. Conclusion: Slc26a2 regulates multiple SO 4 2Ϫ -dependent and SO 4 2Ϫ -independent chondrocyte functions. Significance: The findings should help in understanding aberrant SLC26A2 function in diastrophic dysplasia.

Background: Polycystic kidney disease (PKD) is a hereditary disease characterized by cyst formation in the kidneys bilaterally. It has been observed that semaphorin-3C (SEMA3C) is overexpressed in polycystic kidney epithelial cells. It is hypothesized that upregulated SEMA3C would contribute to survival of polycystic kidney epithelial cells. Furthermore, as the kidney is a highly vascularized organ, the secreted SEMA3C from PKD epithelial cells will affect glomerular endothelial cells (GECs) in a paracrine manner. Methods: To evaluate the effect of SEMA3C on renal cells, siSEMA3C-treated PKD epithelial cells were used for further analysis, and GECs were exposed to recombinant SEMA3C (rSEMA3C). Also, co-culture and treatment of conditioned media were employed to confirm whether PKD epithelial cells could influence on GECs via SEMA3C secretion. Results: SEMA3C knockdown reduced proliferation of PKD epithelial cells. In case of GECs, exposure to rSEMA3C decreased angiogenesis, which resulted from suppressed migratory ability not cell proliferation. Conclusions: This study indicates that SEMA3C is the aggravating factor in PKD. Thus, it is proposed that targeting SEMA3C can be effective to mitigate PKD.