期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 40, 页码 17379-17384出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1001794107
关键词
Nervous Wreck; synapse formation; Tweek; Wishful Thinking; neuromuscular junction
资金
- Research Fund Katholieke Universiteit Leuven
- Flemish Government
- Francqui Foundation
- Flanders Interuniversity Institute for Biotechnology
- Research Foundation-Flanders (FWO Vlaanderen) [G.0747.09]
- Marie Curie Excellence Grant [MEXT-CT-2006-042267]
- Instituut Voor Wetenschap en Technologie (IWT)
Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)] 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)P(2) as a gatekeeper of neuromuscular junction (NMJ) size. We show that PI(4,5)P(2) 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)P(2)-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)P(2)- 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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