Arp2/3-branched actin regulates microtubule acetylation levels and affects mitochondrial distribution

Abstract

Actin and microtubule cytoskeletons regulate cell morphology, participate in organelle trafficking and function in response to diverse environmental cues. Precise spatial-temporal coordination between these two cytoskeletons is essential for cells to live and move. Here, we report a novel crosstalk between actin and microtubules, in which the branched actin maintains microtubule organization, dynamics and stability by affecting tubulin acetylation levels. We observed that acetylated tubulin significantly decreases upon perturbation of the Arp2/3-branched actin. We subsequently discover that HDAC6 participates in this process by altering its interaction with tubulin and the Arp2/3-stabilizer cortactin. We further identify that the homeostasis of branched actin controls mitochondrial distribution via this microtubule acetylation-dependent mechanism. Our findings shed new light on the integral view of cytoskeletal networks, highlighting post-translational modification as another possible form of cytoskeletal inter-regulation, aside from the established crosstalks through structural connection or upstream signaling pathways.

Local actin nucleation tunes centrosomal microtubule nucleation during passage through mitosis

“…We speculate that this burst of anaphase actin nucleation at centrosomes may cause steric problems, as the two systems compete for physical space around the centrosome. However, in live cells, we cannot rule out the possibility of an indirect crosstalk mediated by either changes in localisation or activity of proteins affecting post‐translational modifications of tubulin during mitotic exit (Shi et al , ). Further, it is possible that the centrosomal actin pool could have a more profound effect depending on the nature of microtubules, i.e.…”

The cell pushes back: The Arp2/3 complex is a key orchestrator of cellular responses to environmental forces

“…Cells migrating in 3D or fibrillar environments show elongated pseudopodia, and their leading edge engages with a network of microtubules as well as Arp2/3-driven actin assembly. A recent study revealed that Arp2/3-generated branched actin could influence microtubule stability through its effect on HDAC-6–mediated acetylation of tubulin [ 20 ]. HDAC6 can be sequestered by cortactin, which is abundant in branched actin networks, thus decreasing the de-acetylation of tubulin and leading to an increase in acetylated, stable tubulin [ 20 ].…”

Skeletal muscle MACF1 maintains myonuclei and mitochondria localization through microtubules to control muscle functionalities

“…Additionally, MACF1 was shown to affect mitochondria localization through nuclear positioning in oocyte egg (Escobar-Aguirre et al, 2017). Interestingly, the interplay between actin branching and microtubule acetylation has been recently pointed out as a mitochondrial distribution keeper in fibroblasts cells (Shi et al, 2019). Increase in microtubule dynamic run against stabilization of microtubules partners, but even worse, it can contribute to the delocalization of few MAPs that preferentially bind to stable microtubule (Gache et al, 2010).…”