TY - JOUR T1 - Molecular pathway underlying bouton stabilization by Semaphorin4D during inhibitory synapse formation JF - bioRxiv DO - 10.1101/100271 SP - 100271 AU - Cátia P. Frias AU - Bresser Tom AU - Scheefhals Lisa AU - Hai Yin Hu AU - Paul M. P. van Bergen en Henegouwen AU - Casper C. Hoogenraad AU - Corette J. Wierenga Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/22/100271.abstract N2 - Changes in inhibitory connections are essential for experience-dependent circuit adaptations, and inhibitory defects may underlie neurodevelopmental diseases such as autism. Inhibitory axons and their presynaptic boutons can undergo rapid changes, but the molecular mechanisms underlying these dynamics and their role in inhibitory synapse formation are currently unclear. By monitoring inhibitory axons over time in organotypic hippocampal slices, we show that stabilization of presynaptic boutons is the first step in inhibitory synapse formation and that this is regulated by the signaling protein Semaphorin4D (Sema4D). Sema4D signaling induces inhibitory bouton stabilization within tens of minutes and can induce local changes in bouton density. We show that this signaling pathway requires ongoing neuronal activity, and involves activation of receptor tyrosine kinase MET and actin remodeling. Our data indicate that actin plays an important role during synapse formation and demonstrate a novel link between MET, a known autism risk factor, and inhibitory presynaptic dynamics. ER -