|The net rate of axonal growth has been proposed to be regulated through a balance between MT- and actin-dependent forces [47, 240, 241]. In axons, “actin is under tension supported in part by microtubules under compression” [234, 242]. Tension is provided by the pull of the growth cone [243,244,–245] and the active contraction of acto-myosin, potentially the actin rings in the axon shaft (Fig. 1; [241, 246]; the stiff nature of cross-linked MT bundles is well suited to oppose compressive forces up to a certain threshold ([240, 247]; Fig. 2).|
In such a balanced system, manipulations such as externally imposed pulling forces [248,249,250,–251] or genetic/pharmacological destabilisation of acto-myosin [234, 235, 252,253,254,–255] clearly modulate axon length or growth. Part of this response is expected to be due to changes in MT assembly, as was found when applying external forces to non-neuronal cells . MTs are not only responders in this context, but can generate forces themselves through dis-/assembly or motor-based sliding [91, 252, 257, 258].
How forces are sensed and translated into compensatory force generation and/or changes in axonal length or growth, remains an important question (see also the last section on cortical anchorage). Potential mechano-responsive mechanisms might involve conformational changes of MTs (single MTs polymerise faster when being pulled in vitro) or changes in the activity status of polymerases such as XMap215 [91, 259]. Furthermore, good experimental support exists for roles of mechano-sensitive calcium channels in axon growth control [260,261,–262] and it remains to be seen whether this occurs through changing MT assembly/disassembly processes.