Journal
JOURNAL OF CELL SCIENCE
Volume 133, Issue 16, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.242883
Keywords
Haptotaxis; Cell guidance; Amoeboid migration; Lymphocyte; Integrins; LFA-1
Categories
Funding
- Agence Nationale de la Recherche [ANR15-CE15-0022, ANR-18-CE09-0029]
- LABEX INFORM
- Region Sud
- Turing Centre for Living systems
- Excellence Initiative of Aix-Marseille Universite (A*MIDEX), a French 'Investissements d'Avenir' programme [A-M-AAP-ID-17-68-170301-11.33-VALIGNAT-HLS-SAT]
- Agence Nationale de la Recherche (ANR) [ANR-18-CE09-0029] Funding Source: Agence Nationale de la Recherche (ANR)
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Cell guidance by anchored molecules, or haptotaxis, is crucial in development, immunology and cancer. Adhesive haptotaxis, or guidance by adhesion molecules, is well established for mesenchymal cells such as fibroblasts, whereas its existence remains unreported for amoeboid cells that require less or no adhesion in order to migrate. We show that, in vitro, amoeboid human T lymphocytes develop adhesive haptotaxis mediated by densities of integrin ligands expressed by high endothelial venules. Moreover, lymphocytes orient towards increasing adhesion with VLA-4 integrins (also known as integrin alpha(4)beta(1)), like all mesenchymal cells, but towards decreasing adhesion with LFA-1 integrins (also known as integrin alpha(L)beta(4)), which has not previously been observed. This counterintuitive 'reverse haptotaxis' cannot be explained by existing mechanisms of mesenchymal haptotaxis involving either competitive anchoring of cell edges under tension or differential integrin-activated growth of lamellipodia, because they both favor orientation towards increasing adhesion. The mechanisms and functions of amoeboid adhesive haptotaxis remain unclear; however, multidirectional integrin-mediated haptotaxis might operate around transmigration ports on endothelia, stromal cells in lymph nodes, and inflamed tissue where integrin ligands are spatially modulated.
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