DEPDC5 regulates the strength of excitatory synaptic transmission by interacting with ubiquitin-specific protease 46.

ABSTRACT: DEP-domain containing-5 (DEPDC5) is part of the GATOR1 complex that inhibits the mechanistic target of rapamycin complex-1 (mTORC1). Loss-of-function mutations in human DEPDC5 are the most common cause of lesional or non-lesional focal epilepsies associated with mTOR hyperactivation. Depdc5 silencing in mature neurons leads to excitation/inhibition imbalance and increased excitatory synapse strength. However, no link exists between mTORC1 hyperactivity and the increased activity of glutamatergic synapses. Here, we found that genetic deletion of Depdc5 in a conditional knockout (cKO) mouse recapitulates the excitatory/inhibitory imbalance observed after transient Depdc5 silencing, with increased strength of excitatory transmission and unaffected inhibitory transmission. In Depdc5 cKO neuron

SUBMITTER: Cerullo MS 

PROVIDER: S-EPMC12165940 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature