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Physiology profile

Associate Professor Fiona McDonald

PositionAssociate Professor / Head of the Department of Physiology
DepartmentDepartment of Physiology
QualificationsDPhil(Oxon)
Research summaryKidney control of blood pressure
Teaching
  • PHSL 233 Epithelial signalling and polarity
  • PHSL 343 Endocytosis in epithelia; trafficking pathways of the epithelial sodium channel; polycystic kidney disease
  • PHSL 473 Kidney control of blood pressure
Memberships
  • Member of Kidney in Health and Disease Research Group
  • New Zealand Association of Scientists
  • NZ Biochemistry and Molecular Biology Society
  • Physiological Society of NZ
  • Dunedin Company of Physiologists

Research

How do proteins find their way to their correct location in a cell? What factors control this ‘protein trafficking’ process? Using the epithelial sodium channel (ENaC), essential for kidney control of blood pressure, we have shown that ubiquitin pathway proteins control the number of ENaCs at the cell surface resulting in changes in Na+ absorption. As part of a protein interaction screen we discovered that COMMD family proteins also regulate ENaC trafficking. The mechanisms and implications of this pathway are under investigation.

Pancreatic acinar cells are responsible for digestive enzyme secretion subsequently necessary for breakdown of ingested food. Unregulated activation of digestive enzymes in the acinar cells of the pancreas can cause cell damage, in a process called pancreatitis. The COMMD10 protein is highly expressed in pancreas and has links to the protein secretory pathway; we are currently investigating the role of COMMD10 in the production and secretion of digestive enzymes from pancreatic acinar cells.

Publications

Cheung, T. T., Ismail, N. A. S., Moir, R., Arora, N., McDonald, F. J., & Condliffe, S. B. (2019). Annexin II light chain p11 interacts with ENaC to increase functional activity at the membrane. Frontiers in Physiology, 10, 7. doi: 10.3389/fphys.2019.00007

Daniels, L. J., Wallace, R. S., Nicholson, O. M., Wilson, G. A., McDonald, F. J., Jones, P. P., Baldi, J. C., Lamberts, R. R., & Erickson, J. R. (2018). Inhibition of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic rats. Cardiovascular Diabetology, 17, 89. doi: 10.1186/s12933-018-0732-x

Ware, A. W., Cheung, T. T., Rasulov, S., Burstein, E., & McDonald, F. J. (2018). Epithelial Na+ Channel: Reciprocal control by COMMD10 and Nedd4-2. Frontiers in Physiology, 9, 793. doi: 10.3389/fphys.2018.00793

Healy, M. D., Hospenthal, M. K., Hall, R. J., Chandra, M., Chilton, M., Tillu, V., … McDonald, F. J., … Ghai, R. (2018). Structural insights into the architecture and membrane interactions of the conserved COMMD proteins. eLIFE, 7, e35898. doi: 10.7554/eLife.35898

Ashley, Z., Mugloo, S., McDonald, F. J., & Fronius, M. (2018). Epithelial Na+ channel differentially contributes to shear stress-mediated vascular responsiveness in carotid and mesenteric arteries from mice. American Journal of Physiology: Heart & Circulatory Physiology, 314(5), H1022-H1032. doi: 10.1152/ajpheart.00506.2017

Journal - Research Article

Cheung, T. T., Ismail, N. A. S., Moir, R., Arora, N., McDonald, F. J., & Condliffe, S. B. (2019). Annexin II light chain p11 interacts with ENaC to increase functional activity at the membrane. Frontiers in Physiology, 10, 7. doi: 10.3389/fphys.2019.00007

Daniels, L. J., Wallace, R. S., Nicholson, O. M., Wilson, G. A., McDonald, F. J., Jones, P. P., Baldi, J. C., Lamberts, R. R., & Erickson, J. R. (2018). Inhibition of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic rats. Cardiovascular Diabetology, 17, 89. doi: 10.1186/s12933-018-0732-x

Ashley, Z., Mugloo, S., McDonald, F. J., & Fronius, M. (2018). Epithelial Na+ channel differentially contributes to shear stress-mediated vascular responsiveness in carotid and mesenteric arteries from mice. American Journal of Physiology: Heart & Circulatory Physiology, 314(5), H1022-H1032. doi: 10.1152/ajpheart.00506.2017

Healy, M. D., Hospenthal, M. K., Hall, R. J., Chandra, M., Chilton, M., Tillu, V., … McDonald, F. J., … Ghai, R. (2018). Structural insights into the architecture and membrane interactions of the conserved COMMD proteins. eLIFE, 7, e35898. doi: 10.7554/eLife.35898

Ware, A. W., Cheung, T. T., Rasulov, S., Burstein, E., & McDonald, F. J. (2018). Epithelial Na+ Channel: Reciprocal control by COMMD10 and Nedd4-2. Frontiers in Physiology, 9, 793. doi: 10.3389/fphys.2018.00793

Daniels, L., Bell, J. R., Delbridge, L. M. D., McDonald, F. J., Lamberts, R. R., & Erickson, J. R. (2015). The role of CaMKII in diabetic heart dysfunction. Heart Failure Reviews, 20(5), 589-600. doi: 10.1007/s10741-015-9498-3

Taura, M., Kudo, E., Kariya, R., Goto, H., Matsuda, K., Hattori, S., … McDonald, F., … Okada, S. (2015). COMMD1/Murr1 reinforces HIV-1 latent infection through IκB-α stabilization. Journal of Virology, 89(5), 2643-2658. doi: 10.1128/jvi.03105-14

Bobby, R., Medini, K., Neudecker, P., Verne Lee, T., Brimble, M. A., McDonald, F. J., … Dingley, A. J. (2013). Structure and dynamics of human Nedd4-1 WW3 in complex with the αENaC PY motif. Biochimica et Biophysica Acta: Proteins & Proteomics, 1834(8), 1632-1641. doi: 10.1016/j.bbapap.2013.04.031

Liu, Y. F., Swart, M., Ke, Y., Ly, K., & McDonald, F. J. (2013). Functional interaction of COMMD3 and COMMD9 with the epithelial sodium channel. American Journal of Physiology: Renal Physiology, 305(1), F80-F89. doi: 10.1152/ajprenal.00158.2013

Starokadomskyy, P., Gluck, N., Li, H., Chen, B., Wallis, M., Maine, G. N., … McDonald, F. J., … Burstein, E. (2013). CCDC22 deficiency in humans blunts activation of proinflammatory NF-κβ signaling. Journal of Clinical Investigation, 123(5), 2244-2256. doi: 10.1172/JCI66466

Ly, K., McIntosh, C. J., Biasio, W., Liu, Y., Ke, Y., Olson, D. R., … McDonald, F. J. (2013). Regulation of the delta and alpha epithelial sodium channel (ENaC) by ubiquitination and Nedd8. Journal of Cellular Physiology, 228, 2190-2201. doi: 10.1002/jcp.24390

Chang, T., Ke, Y., Ly, K., & McDonald, F. J. (2011). COMMD1 regulates the delta epithelial sodium channel (δENaC) through trafficking and ubiquitination. Biochemical & Biophysical Research Communications, 411(3), 506-511. doi: 10.1016/j.bbrc.2011.06.149

Wiemuth, D., Lott, J. S., Ly, K., Ke, Y., Teesdale-Spittle, P., Snyder, P. M., & McDonald, F. J. (2010). Interaction of Serum- and Glucocorticoid regulated Kinase 1 (SGK1) with the WW-domains of Nedd4-2 is required for epithelial sodium channel regulation. PLoS ONE, 5(8), e12163. doi: 10.1371/journal.pone.0012163

Walker, R., Spronken-Smith, R., Bond, C., McDonald, F., Reynolds, J., & McMartin, A. (2010). The impact of curriculum change on health sciences first year students' approaches to learning. Instructional Science, 38(6), 707-722. doi: 10.1007/s11251-009-9092-y

Ke, Y., Butt, A. G., Swart, M., Liu, Y.-f., & McDonald, F. J. (2010). COMMD1 down-regulates the epithelial sodium channel through Nedd4-2. American Journal of Physiology: Renal Physiology, 298, F1445-F1456. doi: 10.1152/ajprenal.00257.2009

Bedford, J. J., Weggery, S., Ellis, G., McDonald, F. J., Joyce, P. R., Leader, J. P., & Walker, R. J. (2008). Lithium-induced nephrogenic diabetes insipidus: Renal effects of amiloride. Clinical Journal of the American Society of Nephrology, 3(5), 1324-1331.

Wiemuth, D., Ke, Y., Rohlfs, M., & McDonald, F. J. (2007). Epithelial sodium channel (ENaC) is multi-ubiquitinated at the cell surface. Biochemical Journal, 405, 147-155.

Bromhead, C., Miller, J. H., & McDonald, F. J. (2006). Regulation of T-cadherin by hormones, glucocorticoid and EGF. Gene, 374, 58-67.

Walker, R. J., Weggery, S., Bedford, J. J., McDonald, F. J., Ellis, G., & Leader, J. P. (2005). Lithium-induced reduction in urinary concentrating ability and urinary aquaporin 2 (AQP2) excretion in healthy volunteers. Kidney International, 67, 291-294.

Kivell, B. M., Day, D. J., McDonald, F. J., & Miller, J. H. (2004). Developmental expression of μ and δ opioid receptors in the rat brainstem: Evidence for a postnatal switch in μ isoform expression. Developmental Brain Research, 148, 185-196.

Kivell, B. M., Day, D. J., McDonald, F. J., & Miller, J. H. (2004). Mu and delta opioid receptor immunoreactivity and mu receptor regulation in brainstem cells cultured from late fetal and early postnatal rats. Developmental Brain Research, 149, 9-19.

Biasio, W., Chang, T., McIntosh, C. J., & McDonald, F. J. (2004). Identification of Murr1 as a regulator of the human δ epithelial sodium channel. Journal of Biological Chemistry, 279(7), 5429-5434.

Morrison, P. S., Dobbie, G., & McDonald, F. J. (2003). Research collaboration among university scientists. Higher Education Research & Development, 22(3), 275-296.

Lott, J. S., Coddington-Lawson, S. J., Teesdale-Spittle, P. H., & McDonald, F. J. (2002). A single WW domain is the predominant mediator of the interaction between the human ubiquitin-protein ligase Nedd4 and the human epithelial sodium channel. Biochemical Journal, 361, 481-488.

McDonald, F. J., Western, A. H., McNeil, J. D., Thomas, B. C., Olson, D., & Snyder, P. (2002). Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na+ channel. American Journal of Physiology: Renal Physiology, 283, 431-436.

McDonald, F. J. (2002). Regulation of the epithelial sodium channel by the ubiquitin pathway: implications for hypertension. New Zealand BioScience, 11(3), 8-10.

Kivell, B. M., McDonald, F. J., & Miller, J. H. (2001). Method for serum-free culture of late fetal and early postnatal rat brainstem neurons. Brain Research Protocols, 6(3), 91-99. doi: 10.1016/S1385-299X(00)00037-4

Snyder, P. M., Olson, D. R., McDonald, F. J., & Bucher, D. B. (2001). Multiple WW domains, but not the C2 domain, are required for inhibition of the epithelial Na+ channel by human Nedd4. Journal of Biological Chemistry, 276(30), 28321-28326.

Farr, T. J., Coddington-Lawson, S. J., Snyder, P. M., & McDonald, F. J. (2000). Human Nedd4 interacts with the human epthithelial Na+ channel: WW3 but not WW1 binds to Na+-channel subunits. Biochemical Journal, 345, 503-509.

Kivell, B. M., McDonald, F. J., & Miller, J. H. (2000). Serum-free culture of rat post-natal and fetal brainstem neurons. Developmental Brain Research, 120, 199-210.

McDonald, F. J., Yang, B., Hrstka, R. F., Drummond, H. A., Tarr, D. E., McCray, P. B., … Williamson, R. A. (1999). Disruption of the β subunit of the epithelial Na+ channel in mice: Hyperkalemia and neonatal death associated with a pseudohypoaldosteronism phenotype. PNAS, 96(4), 1727-1731.

McDonald, F. J. (1997). Salt intake and high blood pressure. New Zealand Science Review, 54(3-4), 47-52.

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Journal - Research Other

McDonald, F. J. (2013). COMMD1 and ion transport proteins: What is the COMMection? Focus on "COMMD1 interacts with the COOH terminus of NKCC! in Calu-3 airway epithelial cells to modulate NKCC1 ubiquitination". American Journal of Physiology: Cell Physiology, 305(2), C129-C130. doi: 10.1152/ajpcell.00128.2013

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