WASP is activated by phosphatidylinositol-4,5-bisphosphate to restrict synapse growth in a pathway parallel to bone morphogenetic protein signaling |
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| Authors: | Thang Manh Khuong Ron L P Habets Jan R Slabbaert Patrik Verstreken |
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| Institution: | aDepartment of Molecular and Developmental Genetics, VIB, and;bProgram in Molecular and Developmental Genetics, and Program in Cognitive and Molecular Neuroscience, Center for Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium |
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| Abstract: | Phosphatidylinositol-4,5-bisphosphate PI(4,5)P2] is a membrane lipid involved in several signaling pathways. However, the role of this lipid in the regulation of synapse growth is ill-defined. Here we identify PI(4,5)P2 as a gatekeeper of neuromuscular junction (NMJ) size. We show that PI(4,5)P2 levels in neurons are critical in restricting synaptic growth by localizing and activating presynaptic Wiscott-Aldrich syndrome protein/WASP (WSP). This function of WSP is independent of bone morphogenetic protein (BMP) signaling but is dependent on Tweek, a neuronally expressed protein. Loss of PI(4,5)P2-mediated WSP activation results in increased formation of membrane-organizing extension spike protein (Moesin)-GFP patches that concentrate at sites of bouton growth. Based on pharmacological and genetic studies, Moesin patches mark polymerized actin accumulations and correlate well with NMJ size. We propose a model in which PI(4,5)P2- and WSP-mediated signaling at presynaptic termini controls actin-dependent synapse growth in a pathway at least in part in parallel to synaptic BMP signaling. |
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| Keywords: | Nervous Wreck synapse formation Tweek Wishful Thinking neuromuscular junction |
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