Cecilia Canessa MD

Professor of Cellular and Molecular Physiology and of Medicine (Nephrology)

Research Interests

Renal Function; Epithelial Sodium Channels

Research Summary

The main interest in our laboratory is to elucidate the structure-function and regulation of ion channels from the ENaC/Degenerin family specifically by a set of S/T kinases known as glococorticoid-induced kinases (Sgk). Some of these channels such as ENaC are expressed in kidney where they retain sodium and thereby are key contributors for the maintenance and regulation of blood pressure. The mammalian Degenerins or ASICs are channels expressed in the peripheral and central nervous system where they may regulate membrane excitability and thus contribute to many neuronal processes. We employ a broad variety of approaches that include molecular and cell biological techniques and electrophysiological measurements of channel activity by patch clamp techniques on cultured cells and tissues. We also develop mouse models expressing mutant channels or Sgk kinases to examine the physiological and pathophysiological consequences of altered channel function in blood pressure and in the nervous system.

Extensive Research Description

In our laboratory we examine the structure, function and regulation of two types of sodium channels: the Epithelial Na + Channel (ENaC) and Acid Sensing Ion Channels (ASIC). These proteins are structurally related but serve very different functions. ENaC is expressed in the apical side of epithelial cells involved in sodium absorption such as in kidney, lung and colon. Mutations in the human ENaC genes produce disorders of whole-body sodium balance and are characterized by hypertension or sodium wasting. Our current work centers on mechanisms that regulate activity, expression and traffic of ENaC in epithelial cells specifically, on the role of a kinase known as serum-and glucocorticoid-induced kinase or Sgk1.

The ASICs are expressed in neurons of the central and peripheral nervous systems. External protons gate ASIC but other stimuli are likely to be more important physiological agonists. These channels have been implicated in many functions including nociception, mechanoperception and modulation of synaptic transmission. Our work centers in the elucidation of the biophysical properties and gating of ASICs from many vertebrate species.

We use a broad range of experimental approaches and techniques that include electrophysiology (patch-clamp, two-electrode voltage clamp, short-circuit current), cloning of channels from evolutionary distant species, modifications of channels and their expression in oocytes, cell lines and in mice either trangenics or knockins.

Selected Publications

  • Arteaga MF, Alvarez de la Rosa D, Alvarez JA, Canessa CM. Multiple translational isoforms give functional specificity to serum- and glucocorticoid-induced kinase 1. Mol Biol Cell, 18:2072-80, 2007.
  • Arteaga MF, Wang L, Ravid T, Hochstrasser M, Canessa CM. A short amphipathic helix targets Sgk1 to the ER-associated ubiquitin-conjugation machinery. Proc Natl Acad Sci USA, 103:11178-83, 2006.
  • Zhang P, Sigworth FJ, Canessa CM. Gating of acid-sensitive ion channel-1: Release of Ca2+ block vs. allosteric mechanism. J Gen Physiol, 127:109-17, 2006.
  • Alvarez de la Rosa D, Gimenez I, Forbush B, Canessa CM. SGK1 activates Na+-K+-ATPase in amphibian renal epithelial cells. Am J Physiol Cell Physiol, 290:C492-8, 2006.
  • Coric T, Zheng D, Gerstein M, Canessa CM. Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of residues in the region that follows TM1 in the ectodomain of the channel. J Physiol, 568:725-35, 2005.

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