Intra-axonal Synthesis of SNAP25 Is Required for the Formation of Presynaptic Terminals

• Published in: Cell reports (Cambridge) Vol. 20; no. 13; pp. 3085 - 3098
• Main Authors: Batista, Andreia F.R., Martínez, José C., Hengst, Ulrich
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-09-2017; Cell Press; Elsevier
• Subjects: Animals; axon; Axons; Axons - metabolism; Ciências Médicas; Embryo; Embryo, Mammalian; local protein synthesis; Mammalian; Medicina Básica; presynapse; Presynaptic Terminals; Presynaptic Terminals - metabolism; Rats; Rats, Sprague-Dawley; Science & Technology; SNAP25; synapse formation; synaptic vesicle release; Synaptosomal-Associated Protein 25 - biosynthesis; β-catenin; SNAP25; β-catenin; presynapse; synaptic vesicle release; axon; synapse formation; local protein synthesis
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.08.097

Localized protein synthesis is a mechanism for developing axons to react acutely and in a spatially restricted manner to extracellular signals. As such, it is important for many aspects of axonal development, but its role in the formation of presynapses remains poorly understood. We found that the induced assembly of presynaptic terminals required local protein synthesis. Newly synthesized proteins were detectable at nascent presynapses within 15 min of inducing synapse formation in isolated axons. The transcript for the t-SNARE protein SNAP25, which is required for the fusion of synaptic vesicles with the plasma membrane, was recruited to presynaptic sites and locally translated. Inhibition of intra-axonal SNAP25 synthesis affected the clustering of SNAP25 and other presynaptic proteins and interfered with the release of synaptic vesicles from presynaptic sites. This study reveals a critical role for the axonal synthesis of SNAP25 in the assembly of presynaptic terminals.
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•Protein synthesis is rapidly induced at contact sites with presynaptic organizers•The presynaptic protein SNAP25 is locally synthesized at induced presynaptic sites•Local SNAP25 synthesis is required for formation of presynapses•Inhibition of local SNAP25 synthesis interferes with vesicle release
Batista et al. find that, during the assembly of presynaptic terminals, mRNA translation is upregulated at the nascent presynapses and required for the clustering of presynaptic proteins. Inhibition of local SNAP25 synthesis prevents proper formation of presynaptic terminal and interferes with synaptic vesicle release.