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- Publisher Website: 10.1083/jcb.201406102
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- PMID: 25666809
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Article: F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling
Title | F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling |
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Authors | |
Issue Date | 2015 |
Citation | Journal of Cell Biology, 2015, v. 208, n. 4, p. 443-455 How to Cite? |
Abstract | Mesenchymal cells such as fibroblasts are weakly polarized and reorient directionality by a lamellipodial branching mechanism that is stabilized by phosphoinositide 3-kinase (PI3K) signaling. However, the mechanisms by which new lamellipodia are initiated and directed are unknown. Using total internal reflection fluorescence microscopy to monitor cytoskeletal and signaling dynamics in migrating cells, we show that peripheral F-actin bundles/filopodia containing fascin-1 serve as templates for formation and orientation of lamellipodia. Accordingly, modulation of fascin-1 expression tunes cell shape, quantified as the number of morphological extensions. Ratiometric imaging reveals that F-actin bundles/filopodia play both structural and signaling roles, as they prime the activation of PI3K signaling mediated by integrins and focal adhesion kinase. Depletion of fascin-1 ablated fibroblast haptotaxis on fibronectin but not plateletderived growth factor chemotaxis. Based on these findings, we conceptualize haptotactic sensing as an exploration, with F-actin bundles directing and lamellipodia propagating the process and with signaling mediated by adhesions playing the role of integrator. |
Persistent Identifier | http://hdl.handle.net/10722/311393 |
ISSN | 2023 Impact Factor: 7.4 2023 SCImago Journal Rankings: 3.717 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Johnson, Heath E. | - |
dc.contributor.author | King, Samantha J. | - |
dc.contributor.author | Asokan, Sreeja B. | - |
dc.contributor.author | Rotty, Jeremy D. | - |
dc.contributor.author | Bear, James E. | - |
dc.contributor.author | Haugh, Jason M. | - |
dc.date.accessioned | 2022-03-22T11:53:50Z | - |
dc.date.available | 2022-03-22T11:53:50Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Journal of Cell Biology, 2015, v. 208, n. 4, p. 443-455 | - |
dc.identifier.issn | 0021-9525 | - |
dc.identifier.uri | http://hdl.handle.net/10722/311393 | - |
dc.description.abstract | Mesenchymal cells such as fibroblasts are weakly polarized and reorient directionality by a lamellipodial branching mechanism that is stabilized by phosphoinositide 3-kinase (PI3K) signaling. However, the mechanisms by which new lamellipodia are initiated and directed are unknown. Using total internal reflection fluorescence microscopy to monitor cytoskeletal and signaling dynamics in migrating cells, we show that peripheral F-actin bundles/filopodia containing fascin-1 serve as templates for formation and orientation of lamellipodia. Accordingly, modulation of fascin-1 expression tunes cell shape, quantified as the number of morphological extensions. Ratiometric imaging reveals that F-actin bundles/filopodia play both structural and signaling roles, as they prime the activation of PI3K signaling mediated by integrins and focal adhesion kinase. Depletion of fascin-1 ablated fibroblast haptotaxis on fibronectin but not plateletderived growth factor chemotaxis. Based on these findings, we conceptualize haptotactic sensing as an exploration, with F-actin bundles directing and lamellipodia propagating the process and with signaling mediated by adhesions playing the role of integrator. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Cell Biology | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1083/jcb.201406102 | - |
dc.identifier.pmid | 25666809 | - |
dc.identifier.pmcid | PMC4332254 | - |
dc.identifier.scopus | eid_2-s2.0-84924706005 | - |
dc.identifier.volume | 208 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 443 | - |
dc.identifier.epage | 455 | - |
dc.identifier.eissn | 1540-8140 | - |
dc.identifier.isi | WOS:000349844600008 | - |
dc.identifier.f1000 | 725346834 | - |