Complementary cytoskeletal feedback loops control signal transduction excitability and cell polarity

Jonathan Kuhn, Parijat Banerjee, Andrew Haye, Douglas N. Robinson, Pablo A. Iglesias and Peter N. Devreotes ()
Additional contact information
Jonathan Kuhn: Johns Hopkins School of Medicine
Parijat Banerjee: Johns Hopkins University
Andrew Haye: Johns Hopkins School of Medicine
Douglas N. Robinson: Johns Hopkins School of Medicine
Pablo A. Iglesias: Johns Hopkins University
Peter N. Devreotes: Johns Hopkins School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract To navigate complex environments, cells integrate chemical and mechanical cues through dynamic feedback between signaling networks and the cytoskeleton. Using synthetic tools to manipulate cytoskeletal components in Dictyostelium and human neutrophils, we uncover feedback mechanisms that regulate Ras/PI3K signaling and control front- and back-states of the cell. Increased branched actin and actin polymerization enhance Ras/PI3K activity. Similarly, decreased myosin II assembly also elevates signaling and chemotactic sensitivity. Conversely, inhibiting branched actin increases cortical actin and blocks Ras/PI3K activation—an effect lessened by decreasing filamentous actin or in myosin II-null cells. Activating RacE to increase actin crosslinking suppresses Ras activity without triggering branched actin nucleators, yet promotes spreading and protrusion. These results informed a computational model incorporating positive cytoskeletal feedback loops, which predicts shifts in polarity and migration with cytoskeletal changes. We propose that such feedback locally tunes signal network excitability, enabling cells to navigate tissues, extracellular matrix, and fluid environments.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62799-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62799-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62799-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().