Multiple roles for actin in secretory and endocytic pathways

Chakrabarti, Rajarshi; Lee, Miriam; Higgs, Henry N.

doi:10.1016/j.cub.2021.03.038

Cited by 63 publications

(39 citation statements)

References 215 publications

(278 reference statements)

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“…Dynamic actin polymerization is a vital component of many cellular processes, including cell motility, cytokinesis, endocytosis, vesicle transport, and others. 1,2 Often, the actin filaments created are transient, polymerizing and depolymerizing on a timescale of minutes. These filaments can be used as substrates for myosin-mediated force production or can generated force on their own through polymerization.…”

Section: Introductionmentioning

confidence: 99%

Parallel kinase pathways stimulate actin polymerization at depolarized mitochondria

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Parallel kinase pathways stimulate actin polymerization at depolarized mitochondria

et al. 2022

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“…Another question concerns whether the mitochondrially-associated actin filaments induced during ADA are the cause of the glycolytic increase. While Arp2/3 complex mediates many actin-dependent cellular processes (Chakrabarti et al, 2021; Gautreau et al, 2021), three items suggest that ADA specifically contributes to glycolytic activation. First, inhibition of the mitochondrial sodium-calcium antiporter NCLX by CGP37157 inhibits the glycolytic increase caused by either CCCP or oligomycin stimulation.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction triggers actin polymerization necessary for rapid glycolytic activation

Chakrabarti

Fung

Kang

et al. 2022

Preprint

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Mitochondrial damage represents a dramatic change in cellular homeostasis, necessitating rapid responses. One rapid response is peri-mitochondrial actin polymerization, termed ADA (acute damage-induced actin). The consequences of ADA are not fully understood. Here we show that ADA is necessary for rapid glycolytic activation upon inhibition of mitochondrial ATP production in multiple cells, including mouse embryonic fibroblasts and effector CD8+ T lymphocytes, for which glycolysis is an important source of ATP and biosynthetic molecules. Treatments that induce ADA include CCCP, antimycin A, rotenone, oligomycin, and hypoxia. The Arp2/3 complex inhibitor CK666 or the mitochondrial sodium-calcium exchanger (NCLX) inhibitor CGP37157, applied simultaneously with the ADA stimulus, inhibit both ADA and the glycolytic increase within 5-min, suggesting that ADA is necessary for glycolytic stimulation. Two situations causing chronic reductions in mitochondrial ATP production, ethidium bromide treatment (to deplete mitochondrial DNA) and mutation to the NDUFS4 subunit of complex 1 of the electron transport chain, cause persistent peri-mitochondrial actin filaments of similar morphology to ADA. Both peri-mitochondrial actin loss and a 20% ATP decrease occur within 10 min of CK666 treatment in NDUFS4 knock-out cells. We propose that ADA is necessary for rapid glycolytic activation upon mitochondrial impairment, to re-establish ATP production.

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“…Interestingly, the endocytosis of TrkA is dependent on PI3K signaling (York et al, 2000) as are other forms of receptor endocytosis (Bhattacharya et al, 2016). Some forms of endocytosis are dependent on actin filament dynamics (Chakrabarti et al, 2021) and PI3K-Akt signaling along axons in response to NGF promotes localized polymerization of actin patches preferentially in axonal segments populated by mitochondria (Ketschek and Gallo, 2010). Thus, the failure to phosphorylate Akt at T308 when OxP is suppressed is likely to also prevent TrkA endocytosis, and as shown by the data also the subsequent phosphorylation at S473.…”

Section: Discussionmentioning

confidence: 99%

Bioenergetic Requirements and Spatiotemporal Profile of Nerve Growth Factor Induced PI3K-Akt Signaling Along Sensory Axons

Sainath

Gallo

2021

Front. Mol. Neurosci.

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Nerve Growth Factor (NGF) promotes the elaboration of axonal filopodia and branches through PI3K-Akt. NGF activates the TrkA receptor resulting in an initial transient high amplitude burst of PI3K-Akt signaling followed by a maintained lower steady state, hereafter referred to as initiation and steady state phases. Akt initially undergoes phosphorylation at T308 followed by phosphorylation at S473, resulting in maximal kinase activation. We report that during the initiation phase the localization of PI3K signaling, reported by visualizing sites of PIP3 formation, and Akt signaling, reflected by Akt phosphorylation at T308, correlates with the positioning of axonal mitochondria. Mitochondrial oxidative phosphorylation but not glycolysis is required for Akt phosphorylation at T308. In contrast, the phosphorylation of Akt at S473 is not spatially associated with mitochondria and is dependent on both oxidative phosphorylation and glycolysis. Under NGF steady state conditions, maintenance of phosphorylation at T308 shows dual dependence on oxidative phosphorylation and glycolysis. Phosphorylation at S473 is more dependent on glycolysis but also requires oxidative phosphorylation for maintenance over longer time periods. The data indicate that NGF induced PI3K-Akt signaling along axons is preferentially initiated at sites containing mitochondria, in a manner dependent on oxidative phosphorylation. Steady state signaling is discussed in the context of combined contributions by mitochondria and the possibility of glycolysis occurring in association with endocytosed signalosomes.

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Multiple roles for actin in secretory and endocytic pathways

Cited by 63 publications

References 215 publications

Parallel kinase pathways stimulate actin polymerization at depolarized mitochondria

Parallel kinase pathways stimulate actin polymerization at depolarized mitochondria

Mitochondrial dysfunction triggers actin polymerization necessary for rapid glycolytic activation

Bioenergetic Requirements and Spatiotemporal Profile of Nerve Growth Factor Induced PI3K-Akt Signaling Along Sensory Axons

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