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A presynaptic spectrin network controls active zone assembly and neurotransmitter release

By Qi Wang, Lindsey Friend, Rosario Vicidomini, Tae Hee Han, Peter Nguyen, Chun-Yuan Ting, Mihaela Serpe

Posted 21 Oct 2019
bioRxiv DOI: 10.1101/812032

We have previously reported that Drosophila Tenectin (Tnc) recruits α PS2/βPS integrin to ensure structural and functional integrity at larval NMJs (Wang et al., 2018). In muscles, Tnc/integrin engages the spectrin network to regulate the size and architecture of synaptic boutons. In neurons, Tnc/integrin controls neurotransmitter release. Here we show that presynaptic Tnc/integrin modulates the synaptic accumulation of key active zone components, including the Ca2+ channel Cac and the active zone scaffold Brp. Presynaptic α-Spectrin appears to be both required and sufficient for the recruitment of Cac and Brp. We visualized the endogenous α-Spectrin and found that Tnc controls spectrin recruitment at synaptic terminals. Thus, Tnc/integrin anchors the presynaptic spectrin network and ensures the proper assembly and function of the active zones. Since pre- and postsynaptic Tnc/integrin limit each other, we hypothesize that this pathway links dynamic changes within the synaptic cleft to changes in synaptic structure and function.

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