Seizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3

ABSTRACT: Seizure protein 6 (SEZ6) is required for development and maintenance of the nervous system, is a major substrate of the protease BACE1 and is linked to Alzheimer's disease (AD) and psychiatric disorders, but its molecular functions are not well understood. Here we demonstrate that SEZ6 controls glycosylation and cell surface localization of kainate receptors composed of GluK2/3 subunits. Loss of SEZ6 reduced surface levels of GluK2/3 in primary neurons and reduced kainate-evoked currents in CA1 pyramidal neurons in acute hippocampal slices. Mechanistically, loss of SEZ6 in vitro and in vivo prevented modification of GluK2/3 with the human natural killer-1 (HNK-1) glycan, a modulator of GluK2/3 function. SEZ6 interacted with GluK2 through its ectodomain and promoted post-endoplasmic reticul

SUBMITTER: Mrs. Martina Pigoni 

PROVIDER: S-SCDT-EMBOJ-2019-103457 | biostudies-other |

REPOSITORIES: biostudies-other