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Abstract: FR-PO330

Succinate Signaling Regulates Succinate Transport

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Shimshilashvili, Liana, Ben Gurion University of the Negev, Beer sheva, Israel
  • Khamaysi, Ahlam, Ben Gurion University of the Negev, Beer sheva, Israel
  • Ohana, Ehud, Ben Gurion university of the Negev, Beer sheva, Israel
Background

The SUCNR1 acts as an extracellular succinate sensor and is widely expressed in a variety of epithelial tissues namely the kidney, liver and the intestine. SUCNR1 is a Gq coupled receptor which regulates renin secretion when stimulated in the macula densa. In general, Gq coupled receptors elevate intracellular IP3, that subsequently binds the IP3 receptor (IP3R) and releases IRBIT. IRBIT is the master transport regulator, interacting and modulating the NBC, Slc26a6 and succinate transporters. Here we asked whether succinate receptor stimulation regulates succinate transport via the IP3- IRBIT pathway.

Methods

We monitored SUCNR1 and NaDC-1 mediated succinate transport using fluorescent ion imaging and electrophysiological measurements, respectively. Protein expression was monitored using biochemical techniques.

Results

We found that SUCNR1 activity in transfected human embryonic kidney cells (HEK293) results in intracellular Ca2+ release, which is abolished by PLC inhibitor. Moreover, SUCNR1 activity is desensitized by succinate overstimulation. SUCNR1 is expected to result in IRBIT release. We found that IRBIT interacts with the succinate transporter NaDC-1 and regulates succinate transport.

Conclusion

Together, our results suggest that succinate signaling may regulate succinate transport across cellular membranes.