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Fo\u0308rster resonance energy transfer (FRET) imaging by fluorescence lifetime microscopy (FLIM) reveals an NGF-induced interaction of activated TC10 with Exo70. Expression of dominant-negative mutants and siRNA-mediated knockdown implicates N-WASP in NGF-induced Exo70-TC10-mediated membrane protrusion. However, FRET imaging of N-WASP activation levels of cells expressing Exo70 and\/or constitutively active TC10 reveals that this complex locally antagonises the NGF-induced activation of N-WASP in membrane protrusions. Experiments involving siRNA-mediated knockdown of Cdc42 and overexpression of constitutively active Cdc42 confirm that the Exo70-TC10 complex mainly targets the NGF-induced Cdc42-dependent activation of N-WASP. Our results show that Exo70 is responsible for the correct targeting of the Exo70-TC10 complex to sites of membrane protrusion. The functional uncoupling between both pathways represents a novel regulatory mechanism that enables switching between morphologically distinct \u2013 Cdc42- or TC10-dominated \u2013 forms of cellular membrane outgrowth.<\/jats:p>","DOI":"10.1242\/jcs.03475","type":"journal-article","created":{"date-parts":[[2007,7,18]],"date-time":"2007-07-18T00:40:46Z","timestamp":1184719246000},"page":"2694-2705","source":"Crossref","is-referenced-by-count":38,"title":["An NGF-induced Exo70-TC10 complex locally antagonises Cdc42-mediated activation of N-WASP to modulate neurite outgrowth"],"prefix":"10.1242","volume":"120","author":[{"given":"Dagmar","family":"Pommereit","sequence":"first","affiliation":[{"name":"European Neuroscience Institute-Go\u0308ttingen, Cell Biophysics Group and DFG Research Center for Molecular Physiology of the Brain (CMPB), D-37073 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred S.","family":"Wouters","sequence":"additional","affiliation":[{"name":"European Neuroscience Institute-Go\u0308ttingen, Cell Biophysics Group and DFG Research Center for Molecular Physiology of the Brain (CMPB), D-37073 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042520020028700_REF1","doi-asserted-by":"crossref","unstructured":"Abe, T., Kato, M., Miki, H., Takenawa, T. and Endo, T. 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