Syntaxin-1/TI-VAMP SNAREs interact with Trk receptors and are required for neurotrophin-dependent outgrowth
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Giulia Fuschini1,2,*, Tiziana Cotrufo1,2,3,*, Oriol Ros1,2, Ashraf Muhaisen1,3, Rosa Andrés1,2, Joan X. Comella2,3 and Eduardo Soriano1,2,3,4
1Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain
2Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, 28031 Madrid, Spain
3Vall d'Hebron Institute of Research (VHIR), 08035 Barcelona, Spain
4Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
*These authors contributed equally to this work
Eduardo Soriano, email: [email protected]
Tiziana Cotrufo, email: [email protected]
Keywords: SNARE proteins; Trk receptors; exocytosis; neurotrophins; neuronal outgrowth
Received: September 25, 2017 Accepted: October 24, 2018 Published: November 13, 2018
SNARE proteins are essential components of the machinery that regulates vesicle trafficking and exocytosis. Their role is critical for the membrane-fusion processes that occur during neurotransmitter release. However, research in the last decade has also unraveled the relevance of these proteins in membrane expansion and cytoskeletal rearrangements during developmental processes such as neuronal migration and growth cone extension and attraction. Neurotrophins are neurotrophic factors that are required for many cellular functions throughout the brain, including neurite outgrowth and guidance, synaptic formation, and plasticity. Here we show that neurotrophin Trk receptors form a specific protein complex with the t-SNARE protein Syntaxin 1, both in vivo and in vitro. We also demonstrate that blockade of Syntaxin 1 abolishes neurotrophin-dependent growth of axons in neuronal cultures and decreases exocytotic events at the tip of axonal growth cones. 25-kDa soluble N-ethylmaleimide-sensitive factor attachment protein and Vesicle-associated membrane protein 2 do not participate in the formation of this SNARE complex, while tetanus neurotoxin-insensitive vesicle-associated membrane protein interacts with Trk receptors; knockdown of this (v) SNARE impairs Trk-dependent outgrowth. Taken together, our results support the notion that an atypical SNARE complex comprising Syntaxin 1 and tetanus neurotoxin-insensitive vesicle-associated membrane protein is required for axonal neurotrophin function.
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