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Rajini Rao

Link to Lab Homepage
Department AffiliationPrimary: Physiology
Secondary:
RankProfessor
Emailrrao@jhmi.edu
Mailing Address725 N. Wolfe St.
WBSB 201
Baltimore, MD 21205
Rajini Rao Photo

Discovery and molecular mechanisms of novel ion transporters.

The Rao laboratory uses yeast as a model organism to study novel ion transporters in the endomembranes of cells. Much of our work focuses on the secretory pathway Ca2+/Mn2+-ATPase and the endosomal Na+/H+ exchanger. Both were first discovered in yeast and shown to be founding members of new gene families that are ubiquitously distributed in eukaryotes. Our studies have uncovered fundamental mechanisms in salt tolerance, calcium signaling, manganese detoxification, pH control and vesicle trafficking that are common to yeast, plants and animals. More recently, we have extended our studies to mammalian systems where they have relevance to human health and disease. Future directions of our research will see the increasing use of high throughput phenotype screening and genome-wide approaches to analyze structure-function correlates in ion transporters, and to uncover the functions of novel genes in ion homeostasis, antifungal drug sensitivity and cell signaling pathways. For information on specific projects and references, please visit our website.

Zhang YQ and Rao R. (2008) A spoke in the wheel: Calcium spikes disrupt yeast cell cycle. Cell Cycle 7(7): 870-3.
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Faddy HM, Smart CE, Xu R, Lee GY, Kenny PA, Feng M, Rao R, Brown MA, Bissell MJ, Roberts-Thomson SJ, Monteith GR. (2008) Localization of plasma membrane and secretory calcium pumps in the mammary gland. Biochem Biophys Res Commun 369(3): 977-87.
Pubmed Reference

Muend S and Rao R. (2008) Fungicidal activity of amiodarone is tightly coupled to calcium influx. FEMS Yeast Res 8(3): 425-31.  

Xiang M, Feng M, Muend S, and Rao R. (2007) A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension. Proc Natl Acad Sci USA 104(47): 18677-81.
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Zhang YQ and Rao R. (2007) Global disruption of cell cycle progression and nutrient response by the antifungal agent amiodarone. J Biol Chem 282(52): 37844-53.
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Yadav J, Muend S, Zhang Y, and Rao R. (2007) A phenomics approach in yeast links proton and calcium pump function in the Golgi. Mol Biol Cell 18(4): 1480-9.
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Hill JK, Brett CL, Chyou A, Kallay LM, Sakaguchi M, Rao R, and Gillespie PG. (2006) Vestibular hair bundles control pH with (Na+, K+)/H+ exchangers NHE6 and NHE9. J Neurosci 26(39): 9944-55.
PubMed Reference

Mukherjee S, Kallay L, Brett CL, Rao R. (2006) Mutational analysis of the intramembranous H10 loop of yeast Nhx1 reveals a critical role in ion homeostasis and vesicle trafficking. Biochem J 398(1): 97-105.
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Brett CL, Donowitz M, and Rao R. (2006) Does the proteome encode organellar pH? FEBS Lett 580(3): 717-9.
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Xiang M, Mohamalawari D, and Rao R. (2005) A novel isoform of the secretory pathway Ca2+, Mn2+-ATPase, hSPCA2, has unusual properties and is expressed in brain. J Biol Chem 280(12): 11608-14.
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Brett CL, Tukaye DN, Mukherjee S, and Rao R. (2005) The yeast endosomal Na+(K+)/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking. Mol Biol Cell 16(3): 1396-405.
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Brett CL, Donowitz M, and Rao R. (2005) The evolutionary origins of eukaryotic sodium/proton exchangers. Am J Physiol Cell Physiol 288(2): C223-39. [Supplementary Info: Table 1S.html Fig 1S.png (136k) Fig 2S.png (544k) Fig 3S.png (340k) Fig 4S.png (660k)]
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Rao R, and Inesi G. (2004) Inherited Disorders of Calcium ATPases: Role in Health and Disease. Membrane Transport Diseases: Molecular basis of inherited transport defects. (S. Broer and C.A. Wagner, eds. Kluwer Academic/Plenum Publishers). 

Ton V-K, and Rao R. (2004) Expression of Hailey-Hailey Disease mutations in yeast. J Invest Dermatol 123(6): 1192-4.
PubMed Reference

Ton V-K, and
Rao R. (2004) Functional expression of heterologous proteins in yeast. Insights into calcium signaling and calcium transporting ATPases. Am J Physiol Cell Physiol 287(3): C580-9.
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Ali R, Brett CL, Mukherjee S, and Rao R. (2004) Inhibition of sodium/proton exchange by a Rab-GTPase activating protein regulates endosomal traffic in yeast. J Biol Chem 279: 4498-4506.
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Mandal D, Rulli S, and Rao R. (2003) Packing interactions between transmembrane helices alter ion selectivity of the yeast Golgi Ca2+/Mn2+-ATPase Pmr1. J Biol Chem 278: 35292-35298.
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Gupta SS, Ton V-K, Beaudry V, Rulli S, Cunningham KW, and Rao R. (2003) Antifungal activity of amiodarone is mediated by disruption of calcium homeostasis. J Biol Chem 278: 28831-28839.
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Cronin SR, Rao R, and Hampton RY. (2002) Cod1p/Spf1p is a P-type ATPase involved in ER function and Ca2+ homeostasis. J Cell Biol 157, 1017-1028.
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Brett CL, Wei Y, Donowitz M, and Rao R. (2002) Human Na+/H+ exchanger NHE6 is found in the recycling endosomes of cells, not mitochondria. Am J Phys Cell Physiol 282(5): C1031-41.
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Ton VK, Mandal D, Vahadji C, and Rao R. (2002) Functional Expression in Yeast of the Human Secretory Pathway Ca2+, Mn2+-ATPase Defective in Hailey-Hailey Disease. J Biol Chem 277(8): 6422-6427.
PubMed Reference

Wells KM, and Rao R. (2001) The yeast Na+/H+ exchanger Nhx1 is an N-linked glycoprotein. Topological implications. J Biol Chem 276: 3401-3407.
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Mandal D, Woolf TB, and Rao R. (2000) Manganese selectivity of the yeast secretory pathway ion pump, Pmr1, is defined by residue Q783 in transmembrane segment 6. Residue D778 is essential for transport. J Biol Chem 275(31): 23933-8.
PubMed Reference

Wei Y, Chen J, Rosas G, Tompkins DA, Holt PA, and Rao R. (2000) Phenotypic screening of mutations in Pmr1, the yeast secretory pathway Ca2+/Mn2+-ATPase, reveals residues critical for ion selectivity and transport. J Biol Chem 275(31): 23927-32.
PubMed Reference

Wei Y, Marchi V, Wang R, and Rao R. (1999) An N-terminal EF hand-like motif modulates ion transport by Pmr1, the yeast Golgi Ca2+/Mn2+-ATPase. Biochemistry 38: 14534-14541.
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Nass R, and Rao R. (1999) The yeast endosomal Na+/H+ Exchanger, Nhx1, confers osmotolerance following acute hypertonic shock. Microbiology 145: 3221-3228.
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Marchi V, Sorin A, Wei Y, and Rao R. (1999) Induction of vacuolar Ca2+-ATPase and H+/Ca2+ exchange activity in yeast mutants lacking Pmr1, the Golgi Ca2+-ATPase. FEBS Lett 454: 181-186.
PubMed Reference

Gaxiola RA, Rao R, Sherman A, Grisafi P, Alper S, and Fink GR. (1999) The Arabidopsis thaliana proton transporters, AtNhx1 and Avp1, can function in cation detoxification in yeast. Proc Natl Acad Sci USA 96: 1480-1485.
PubMed Reference

Nass R, and Rao R. (1998) Novel localization of a Na+/H+ exchanger in a late endosomal compartment of yeast. Implications for vacuole biogenesis. J. Biol. Chem. 273: 21054-21060.
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Nakamoto RK, Verjovski-Almeida S, Allen KE, Ambesi A, Rao R, and Slayman CW. (1998) Substitutions of aspartate 378 in the phosphorylation domain of the yeast PMA1 H+-ATPase disrupt protein folding and biogenesis. J Biol Chem 273: 7338-7344.
PubMed Reference

Nass R, Cunningham KW, and Rao R. (1997) Intracellular sequestration of sodium by a novel Na+/H+ exchanger in yeast is enhanced by mutations in the plasma membrane H+-ATPase. Insights into mechanisms of Na+ tolerance. J Biol Chem 272: 26145-26152.
PubMed Reference

Sorin A, Rosas G, and Rao R. (1997) PMR1, a Ca2+-ATPase in yeast Golgi, has properties distinct from sarco/endoplasmic reticulum and plasma membrane calcium pumps. J. Biol. Chem 272: 9895-9901.
PubMed Reference​

Rao R, and Slayman CW. (1996) The fungal P-ATPases: a functionally diverse family of cation pumps. The Mycota Vol. IV: 29-56 (R. Brambl and G.A. Marzluf, eds. Springer-Verlag, Berlin).

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