Ghrelin receptor constitutive activity reduces surface expression of voltage-gated calcium channels in a CaVβ dependent manner

MUSTAFÁ ER; LÓPEZ SOTO EJ; MARTÍNEZ DAMONTE V; RODRÍGUEZ, SILVIA S.; LIPSCOMBE, DIANE; RAINGO, JESICA

Washington, DC

Congreso; Society for Neurosciences 47th annual meeting; 2017

Society for Neuroscience

Voltage gated calcium channels (CaV) couple plasma membrane voltage changes to calcium influx,triggering calciumdependentprocesses. This sequence of fact is crucial for shaping neuronal activity.Several CaV subtypes exist and they have different time and place specific functions in neurons. Thus,great effort has been devoted to determine what elements can control CaV activity in neurons. In thiscontext, many Gproteincoupled receptors (GPCR) activated cascades have been detected as powerfulCaV activity modulators. On the other hand, data about the control of trafficking and density of CaVsubtypes at specific location on the neuronal plasma membrane are spare. Here we describe that aGPCR that is constitutively active (GHSR1a) in absence of its agonist (ghrelin) inhibits the forwardtrafficking of several CaV subtypes. We found that the mechanism implies retention of the channelcomplexes at the endoplasmic reticulum and the requirement of auxiliary subunit CaVβ. Since the solelyexpression of GHSR1a is enough to control CaV trafficking and this receptor is highly expressed in brainareas controlling food intake, reward and learning and memory, our finding could have a great impact inanimal behavior. Thus, further experiments focusing on the function of each CaV subtype function arerequired to deeply understand the scope of GHSR1a effect on neurons.