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Fig. 8. Model of the proposed functional interplay between Cdc42- and Exo70-TC10-driven signalling pathways leading to neurite outgrowth. Binding of NGF to its plasma membrane receptor (Trk) leads to the coactivation of Cdc42 and TC10 in the plasma membrane and to the membrane recruitment of Exo70. Cdc42 plays a role in the activation of N-WASP, leading to subsequent Arp2/3-mediated actin polymerisation and ensuing membrane protrusion. A complex of Exo70 and active TC10 binds to N-WASP at distinct sites in the plasma membrane and antagonises its activation by the Cdc42 pathway. This favours an Exo70-TC10 dominated pathway to membrane protrusion at these sites. In this pathway, TC10 might employ other actin nucleation promoting factors (NPF) than N-WASP. The morphological outcome of both membrane protrusion pathways is different. We propose that the two GTPase pathways serve different roles that are balanced in neuronal maturation. Cdc42 serves neurite formation/elongation; Exo70-TC10 serves neurite broadening and decoration with spines, to establish neuronal polarity and neuronal communication, respectively. Here, Exo70 bridges actin polymerisation and exocyst function, i.e. exocytic vesicle docking.
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