Monoallelic de novo AJAP1 loss-of-function variants disrupt trans-synaptic control of neurotransmitter release

• DOI: 10.1126/sciadv.adk5462
• Publication Date: 2024-07-10T17:59:51Z
• Authors: Simon Früh; Sami Boudkkazi; Peter Koppensteiner; Vita Sereikaite; Li-Yuan Chen; Diego Fernandez-F...; Pascal D. Rem; Daniel Ulrich; Jochen Schwenk; Ziyang Chen; Elodie Le Monnier; Thorsten Fritzius; Sabrina M. Innocenti; Valérie Besseyrias; Luca Trovò; Michal Stawarski; Emanuela Argilli; Elliott H. Sherr; Bregje van Bon; Erik-Jan Kamsteeg; Maria Iascone; Alba Pilotta; Maria R. Cutrì; Mahshid S. Azamian; Andrés Hernández-...; Seema R. Lalani; Jill A. Rosenfeld; Xiaonan Zhao; Tiphanie P. Vogel; Herda Ona; Daryl A. Scott; Peter Scheiffele; Kristian Strømgaard; Mehdi Tafti; Martin Gassmann; Bernd Fakler; Ryuichi Shigemoto; Bernhard Bettler
• Keywords: Loss function; Neurotransmitter Agents

Adherens junction-associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism not identified. AJAP1 is widely expressed neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses the brain. Here, we show that selectively dendrites trans-synaptically recruits GBRs presynaptic sites of expressing AJAP1. We have identified several monoallelic