Differences in protein mobility between pioneer versus follower growth cones

Abstract

Navigating growth cones need to integrate, process and respond to guidance signals, requiring dynamic information transfer within and between different compartments. Studies have shown that, faced with different navigation challenges, growth cones display dynamic changes in growth kinetics and morphologies. However, it remains unknown whether these are paralleled by differences in their internal molecular dynamics. To examine whether there are protein mobility differences during guidance, we developed multiphoton fluorescence recovery after photobleaching methods to determine molecular diffusion rates in pathfinding growth cones in vivo. Actively navigating growth cones (leaders) have consistently longer recovery times than growth cones that are fasciculated and less actively navigating (followers). Pharmacological perturbations of the cytoskeleton point to actin as the primary modulator of diffusion in differently behaving growth cones. This approach provides a powerful means to quantify mobility of specific proteins in neurons in vivo and reveals that diffusion is important during axon navigation.cytoplasmic dynamics ͉ neuronal migration ͉ two-photon microscopy ͉ zebrafish

Actin Cytoskeleton-Dependent Dynamics of the Human Serotonin1A Receptor Correlates with Receptor Signaling

“…Interestingly, activation of the serotonin 1A receptor has been implicated in neurite outgrowth and neuronal survival (12). These results assume significance in light of a recent report that the protein mobilities are different between navigating and nonnavigating growth cones in neurons, possibly due to differences in the organization of the actin cytoskeleton (62). Moreover, with growing evidence in favor of cAMP transducing specific responses by localized signaling (63), our results raise an interesting possibility of a dynamic system involving the actin cytoskeleton, cAMP, and the serotonin 1A receptor.…”

Nanotopographic Control of Neuronal Polarity

“…4 Neuronal polarity establishment and neurite pathfinding are the most important processes to build a functional tissue during neuronal development and regeneration. 1,5 The function of FAs goes far beyond the simple physical anchorage. 6 Each of the adhesions initially established by a differentiating neuron undergoes a modular maturation and develops from an isotropic focal complex to a mature and anisotropic FA.…”

Translation of the cell adhesion molecule ALCAM in axonal growth cones – regulation and functional importance

“…(A) RGCs were transfected with cDNA encoding the reporter pTimer under the control of the ALCAM 39-UTR. Only axons longer than 150 mm were evaluated so that somatically produced reporter converts from green into red (Terskikh et al, 2000) during diffusion towards the growth cone, which takes more than 4 hours (Kulkarni et al, 2007). The green fluorescent reporter signal in axon and growth cone is higher in RGCs transfected with pTimer under the control of the ALCAM 39-UTR (left) than in RGCs transfected with pTimer lacking the ALCAM 39-UTR (right).…”