4.5 Article

Dynamin activates NO production in rat renal inner medullary collecting ducts via protein-protein interaction with NOS1

Journal

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 301, Issue 1, Pages F118-F124

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00534.2010

Keywords

rat nephron; protein-protein interactions

Funding

  1. National Institutes of Health [HL60653]
  2. National Kidney Foundation

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Hyndman KA, Musall JB, Xue J, Pollock JS. Dynamin activates NO production in rat renal inner medullary collecting ducts via protein-protein interaction with NOS1. Am J Physiol Renal Physiol 301: F118-F124, 2011. First published April 13, 2011; doi: 10.1152/ajprenal.00534.2010.-We hypothesized that nitric oxide synthase (NOS) isoforms may be regulated by dynamin (DNM) in the inner medullary collecting duct (IMCD). The aims of this study were to determine which DNM isoforms (DNM1, DNM2, DNM3) are expressed in renal IMCDs, whether DNM interacts with NOS, whether a high-salt diet alters the interaction of DNM and NOS, and whether DNM activates NO production. DNM2 and DNM3 are highly expressed in the rat IMCD, while DNM1 is localized outside of the IMCD. We found that DNM1 interacts with NOS1 alpha, NOS1 beta, and NOS3 in the inner medulla of male Sprague-Dawley rats on a 0.4% salt diet. DNM2 interacts with NOS1 alpha, while DNM3 interacts with both NOS1 alpha and NOS1 beta. DNM2 and DNM3 do not interact with NOS3 in the rat inner medulla. We did not observe any change in the DNM/NOS interactions with rats on a 4% salt diet after 7 days. Furthermore, NOS1 alpha interacts with DNM2 in mIMCD3 and COS7 cells transfected with NOS1 alpha and DNM2-GFP constructs and the NOS1 reductase domain is necessary for the interaction. Finally, COS7 cells expressing NOS1 alpha or NOS1 alpha/DNM2-GFP had significantly higher nitrite production compared with DNM2-GFP only. Nitrite production was blocked by the DNM inhibitor dynasore or the dominant negative DNM2K44A. Ionomycin stimulation further increased nitrite production in the NOS1 alpha/DNM2-GFP cells compared with NOS1 alpha only. In conclusion, DNM and NOS1 interact in the rat renal IMCD and this interaction leads to increased NO production, which may influence NO production in the renal medulla.

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