Tissue and subcellular localization of mammalian renalase, a FAD-containing protein involved in the pathogenesis of cardiovascular diseases

Renalase is a secretory protein and flavoenzyme that is ubiquitous in vertebrates and conserved in some other phyla. In mammals it has been shown to modulate cardiovascular responses, being particularly active in decreasing catecholaminergic tone, lowering blood pressure, and in protecting the heart against ischemic damage (1). Lowered renalase levels in tissue and plasma might be the basis of the cardiovascular complications observed in chronic kidney disease patients (1). Renalase secretion into the circulation is enhanced in response to stressors such as hypotension, but the molecular mechanism regulating its basal or stimulated secretion are unknown(2). We find that renalase has a signal-sequence, but this sequence is not cleaved prior to its secretion, suggesting that it may traffic in an atypical secretory pathway. In pig kidney, our immunofluorescence studies showed that renalase is exclusively expressed in the proximal tubule. Similar studies in human immortalized HK-2 cells, as well as on pig and mouse primary cell lines, indicated that renalase is preferentially localized in the cytoplasm, where it shows a punctate distribution, suggestive of an organelle association. The identification of these subcellular compartment(s), mechanism of association, and renalase’s mechanism of secretion are underway. This knowledge could lead to novel therapies for cardiovascular and kidney diseases (3). This work has been supported by travel fellowships granted by the Italian Society of Biochemistry and Molecular Biology (SIB) and by the Consorzio Interuniversitario di Biotecnologie to S. Baroni. 1. Desir GV. Curr Opin Nephrol Hypertens. 2011; 20: 31-6. 2. Milani M, et al. J Mol Biol. 2011; 411: 463-73. 3. Unger T, et al. Eur Heart J. 2011; 32: 2739-47.