Dynamin-2 is a novel NOS1β interacting protein and negative regulator in the collecting duct

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Kelly A HyndmanJennifer S Pollock

Abstract

Nitric oxide synthase 1 (NOS1)-derived nitric oxide (NO) production in collecting ducts is critical for maintaining fluid-electrolyte balance. Rat collecting ducts express both the full-length NOS1α and its truncated variant NOS1β, while NOS1β predominates in mouse collecting ducts. We reported that dynamin-2 (DNM2), a protein involved in excising vesicles from the plasma membrane, and NOS1α form a protein-protein interaction that promotes NO production in rat collecting ducts. NOS1β was found to be highly expressed in human renal cortical/medullary samples; hence, we tested the hypothesis that DNM2 is a positive regulator of NOS1β-derived NO production. COS7 and mouse inner medullary collecting duct-3 (mIMCD3) cells were transfected with NOS1β and/or DNM2. Coimmunoprecipitation experiments show that NOS1β and DNM2 formed a protein-protein interaction. DNM2 overexpression decreased nitrite production (index of NO) in both COS7 and mIMCD-3 cells by 50-75%. mIMCD-3 cells treated with a panel of dynamin inhibitors or DNM2 siRNA displayed increased nitrite production. To elucidate the physiological significance of IMCD DNM2/NOS1β regulation in vivo, flox control and CDNOS1 knockout mice were placed on a high-salt diet, and freshly ...Continue Reading

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Citations

Oct 22, 2016·American Journal of Physiology. Renal Physiology·Yang GaoDonald E Kohan
Jun 10, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Kelly Anne HyndmanJennifer S Pollock
Aug 2, 2018·Biological Chemistry·Susanne Eschenburg, Thomas F Reubold
Jun 27, 2019·American Journal of Physiology. Renal Physiology·Luciano D Mendoza, Kelly A Hyndman
Oct 20, 2021·Physiological Reports·Kelly A HyndmanJennifer S Pollock

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