Regulation of synaptic inhibition by phospho dependent binding of the AP2 complex to a YECL motif in the GABAA receptor gamma2 subunit

The regulation of the number of amp; 947;2 subunit containing GABAA receptors GABAARs present at synapses is critical for correct synaptic inhibition and animal behavior. This regulation occurs, in part, by the controlled removal of receptors from the membrane in clathrin coated vesicles, but it remains unclear how clathrin recruitment to surface amp; 947;2 subunit containing GABAARs is regulated. Here, we identify a amp; 947;2 subunit specific Yxx amp; 966; type binding motif for the clathrin adaptor protein, AP2, which is located within a site for amp; 947;2 subunit tyrosine phosphorylation. Blocking GABAAR AP2 interactions via this motif increases synaptic responses within minutes. Crystallographic and biochemical studies reveal that phosphorylation of the Yxx amp; 966; motif inhibits AP2 binding, leading to increased surface receptor number. In addition, the crystal structure provides an explanation for the high affinity of this motif for AP2 and suggests that amp; 947;2 subunit containing heteromeric GABAARs may be internalized as dimers or multimers. These data define a mechanism for tyrosine kinase regulation of GABAAR surface levels and synaptic inhibitio

Search for multimessenger sources of gravitational waves and high-energy neutrinos with Advanced LIGO during its first observing run, ANTARES, and IceCube

Astrophysical sources of gravitational waves, such as binary neutron star and black hole mergers or core-collapse supernovae, can drive relativistic outflows, giving rise to non-thermal high-energy emission. High-energy neutrinos are signatures of such outflows. The detection of gravitational waves and high-energy neutrinos from common sources could help establish the connection between the dynamics of the progenitor and the properties of the outflow. We searched for associated emission of gravitational waves and high-energy neutrinos from astrophysical transients with minimal assumptions using data from Advanced LIGO from its first observing run O1, and data from the Antares and IceCube neutrino observatories from the same time period. We focused on candidate events whose astrophysical origins could not be determined from a single messenger. We found no significant coincident candidate, which we used to constrain the rate density of astrophysical sources dependent on their gravitational-wave and neutrino emission processes