Control of microtubules in neuronal processes by profilin 1 and actomyosin.

In addition to its well-established role in actin assembly, Profilin 1 (PFN1) has been shown to bind to tubulin and alter the polymerization of microtubules. However, whether PFN1's predominant control over microtubules in cells occurs through direct regulation of tubulin or indirectly through the polymerization of actin has yet to be determined. Here we manipulated PFN1 expression, actin filament assembly, and actomyosin contractility and showed that reducing any of these increases the number and acetylation of microtubules, with the effect being significantly more pronounced in neuronal processes. Changes to microtubules are reversible if actomyosin contractility is restored, arguing that PFN1's regulation of microtubules occurs principally through actin. Moreover, the altered microtubules in neuronal processes resulting from PFN1 depletion cause significant changes to microtubule-based transport, mimicking phenotypes that are linked to neurodegenerative disease. Thus, defects in actin dynamics cause a compensatory response in other cytoskeleton components, profoundly effecting cellular function.