Lamellipodia are crucial for haptotactic sensing and response
| Autor: | James G. Alb, Brian Kuhlman, Alicia C. Tagliatela, Daniel J. Marston, Jason M. Haugh, Maddy Parsons, Irina P. Lebedeva, James E. Bear, Seth P. Zimmerman, Jeremy D. Rotty, Elizabeth M. Haynes, Sreeja B. Asokan, Samantha J. King, Devon R. Blake, Norman E. Sharpless, Heath E. Johnson |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell RAC1 Models Biological Actin-Related Protein 2-3 Complex Haptotaxis Extracellular matrix Mice 03 medical and health sciences medicine Animals Guanine Nucleotide Exchange Factors T-Lymphoma Invasion and Metastasis-inducing Protein 1 Pseudopodia Actin Focal Adhesions biology Chemotaxis Integrin beta1 Cell migration Cell Biology Fibroblasts Lamellipodia Actins Fibronectins Wiskott-Aldrich Syndrome Protein Family rac GTP-Binding Proteins Cell biology Fibronectin src-Family Kinases 030104 developmental biology medicine.anatomical_structure Focal Adhesion Protein-Tyrosine Kinases Immunology biology.protein Lamellipodium Arp2/3 Wiskott-Aldrich Syndrome Protein Directed migration Research Article Signal Transduction |
| Zdroj: | King, S J, Asokan, S B, Haynes, E M, Zimmerman, S P, Rotty, J D, Alb, J G, Tagliatela, A, Blake, D R, Lebedeva, I P, Marston, D, Johnson, H E, Parsons, M, Sharpless, N E, Kuhlman, B, Haugh, J M & Bear, J E 2016, ' Lamellipodia are crucial for haptotactic sensing and response ', Journal of Cell Science, vol. 129, no. 12, pp. 2329-2342 . https://doi.org/10.1242/jcs.184507 |
| DOI: | 10.1242/jcs.184507 |
| Popis: | Haptotaxis is the process by which cells respond to gradients of substrate-bound cues, such as extracellular matrix proteins (ECM); however, the cellular mechanism of this response remains poorly understood and has mainly been studied by comparing cell behavior on uniform ECMs with different concentrations of components. To study haptotaxis in response to gradients, we utilized microfluidic chambers to generate gradients of the ECM protein fibronectin, and imaged the cell migration response. Lamellipodia are fan-shaped protrusions that are common in migrating cells. Here, we define a new function for lamellipodia and the cellular mechanism required for haptotaxis – differential actin and lamellipodial protrusion dynamics lead to biased cell migration. Modest differences in lamellipodial dynamics occurring over time periods of seconds to minutes are summed over hours to produce differential whole cell movement towards higher concentrations of fibronectin. We identify a specific subset of lamellipodia regulators as being crucial for haptotaxis. Numerous studies have linked components of this pathway to cancer metastasis and, consistent with this, we find that expression of the oncogenic Rac1 P29S mutation abrogates haptotaxis. Finally, we show that haptotaxis also operates through this pathway in 3D environments. |
| Databáze: | OpenAIRE |
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