INVESTIGADORES
BOUZAT Cecilia Beatriz
congresos y reuniones científicas
Título:
Why is the alpha7 nicotinic receptor so complex and unique?
Autor/es:
BOUZAT, C.
Reunión:
Conferencia; Frontiers in Bioscience 3.Instituto de Investigación en Biomedicina de Buenos Aires-Instituto Partner de la Sociedad Max Planck. (IBIOBA-MPSP).; 2018
Resumen:
The α7 nicotinic receptor (nAChR), which is the homomeric member of the family, is involved in neurological, psychiatric and inflammatory disorders. Enhancement of α7 function by positive allosteric modulators (PAMs) is a promising therapeutic strategy to improve cognitive deficits and for inflammatory processes. By single channel recording we deciphered activation properties of α7 and mechanisms of PAM action. We found that PAMs enhance open-channel lifetime and produce episodes of successive openings of different durations. We identified the structural determinants for their allosteric actions and the temperature sensitivity of potentiation. New evidence has demonstrated the expression in brain of a novel heteromeric α7β2 receptor whose role and functional properties remain unknown. To establish its functional stoichiometry, we used two different experimental approaches, concatemeric technology and the electrical fingerprinting strategy with an α7 subunit tagged with a reporter mutation. Our results revealed the stoichiometry of functional heteromeric receptors, the contribution of β2 subunit to channel kinetics and ion permeability, and the action of α7 PAMs at α7β2. This information is required for differentiating homomeric from heteromeric receptors in native cells and for understanding their distinct roles. We also determined that an α7 truncated subunit, which is only found in humans, is capable of forming heteromeric receptors with α7 and acts as a negative modulator. The understanding of α7 function from its fundamental level provides information for rational drug design.