Figure 5

Proposed model for XMAP215 function in neurons. (A) Cartoon schematic of proposed functions of XMAP215 in wild-type conditions. Our data suggests that XMAP215 functions to mediate MT-F-actin coupling in both axons and growth cones. In the axon, as XMAP215 knockdown (KD) leads to a myosin II-dependent increase in axon retraction, this implicates XMAP215 as part of the machinery that stabilizes MT forces to oppose the actomyosin-mediated retraction (1). In the growth cone, XMAP215 KD leads to an increase in anterograde MT sliding (2) and a loss of colinearity of MT trajectories (3). As MT translocation rates and trajectory coherence within growth cones are strongly affected by coupling to F-actin retrograde flow, this data suggests that XMAP215 also contributes to the linkages between MTs and F-actin in the growth cone. These novel functions that we propose are in addition to the canonical function of XMAP215 - driving processive MT polymerization (4). (B) Consequences of XMAP215 KD. When XMAP215 is knocked down approximately 70%, this results in disruptions to all four functions, as described in the figure.