ArticleFrontiers in cellular neuroscience2018
Model for Coordination of Microtubule and Actin Dynamics in Growth Cone Turning.
Article in Frontiers in cellular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 9 citations in OpenAlex.
- Prostaglandin E2 Increases Neurite Length and the Formation of Axonal Loops, and Regulates Cone Turning in Differentiating NE4C Cells Via PKA.Cellular and molecular neurobiology · 2022Article
- Local Translation in Nervous System Pathologies.Frontiers in integrative neuroscience · 2021Review
- Bridging the Gap: The Importance of TUBA1A α-Tubulin in Forming Midline Commissures.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the developing nervous system, axons are guided to their synaptic targets by motile structures at the axon tip called growth cones, which reorganize their cytoskeleton in order to steer in response to chemotactic cues. Growth cone motility is mediated by an actin-adhesion "clutch" mechanism, in which mechanical attachment to a substrate, coupled with polarized actin growth, produces leading-edge protrusion. Several studies suggest that dynamic microtubules (MTs) in the growth cone periphery play an essential role in growth cone steering. It is not yet well-understood how the MT cytoskeleton and the dynamic actin-adhesion clutch system are coordinated to promote growth cone navigation. I introduce an experimentally motivated stochastic model of the dynamic reorganization of the growth cone cytoskeleton in response to external guidance cues. According to this model, asymmetric decoupling of MTs from actin retrograde flow leads to a local influx of MTs to the growth cone leading edge, and the leading-edge MT accumulation is amplified by positive feedback between MTs and the actin-adhesion clutch system. Local accumulation of MTs at the leading edge is hypothesized to increase actin adhesion to the substrate, which attenuates actin retrograde flow and promotes leading-edge protrusion. Growth cone alignment with the chemotactic gradient is predicted to be most effective for intermediate levels of sensitivity of the adhesion strength to the presence of leading-edge MTs. Quantitative predictions of the MT distribution and the local rate of retrograde actin flow will allow the hypothetical positive feedback mechanism to be experimentally tested.
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