Open AccessWASP is activated by phosphatidylinositol-4,5-bisphosphate to restrict synapse growth in a pathway parallel to bone morphogenetic protein signaling
Author(s) -
Thang M. Khuong,
R. Habets,
Jan R. Slabbaert,
Patrik Verstreken
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1001794107
Subject(s) - microbiology and biotechnology , phosphatidylinositol 4,5 bisphosphate , synapse , phosphatidylinositol , biology , bone morphogenetic protein , signal transduction , neuromuscular junction , actin , neuroscience , biochemistry , gene
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.