3 years ago

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

Diane Lipscombe, Valentina Martínez Damonte, Jesica Raingo, Silvia S Rodríguez, Eduardo J López Soto, Emilio R Mustafá
Voltage gated calcium (CaV) channels couple membrane depolarization to calcium influx, triggering a range of calcium-dependent cellular processes. CaV channels are therefore critical in shaping neuronal activity and function, depending on their individual temporal and spatial properties. Furthermore, many neurotransmitters and drugs that act through G protein coupled receptors (GPCRs), modulate neuronal activity by altering the expression, trafficking, or function of CaV channels. GPCR-dependent mechanisms that down regulate CaV channel expression levels are observed in many neurons but are, by comparison, less studied. Here we show that the growth hormone secretagogue receptor type 1a (GHSR), a GPCR, can inhibit the forwarding trafficking of several CaV subtypes even in the absence of agonist. This constitutive form of GPCR inhibition of CaV channels depends on the presence of a CaVβ subunit. CaVβ subunits displace CaVα1 subunits from the endoplasmic reticulum. The actions of GHSR on CaV channels trafficking suggest a role for this signaling pathway in brain areas that control food intake, reward and learning and memory.

Publisher URL: http://doi.org/10.1242/jcs.207886

DOI: 10.1242/jcs.207886

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