4.7 Article

cAMP Bursts Control T Cell Directionality by Actomyosin Cytoskeleton Remodeling

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出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.633099

关键词

lymphocyte; migration; cAMP; actomyosin; chemokine

资金

  1. Association pour la Recherche contre le Cancer [PJA 20131200379]
  2. CNRS
  3. INSERM
  4. Universite de Paris
  5. Ministere de l'Enseignement Superieur et de la Recherche
  6. Cochin Institute (PIC Program)

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The migration of T lymphocytes requires dynamic changes in cAMP levels, which in turn promote actomyosin redistribution to modify cell trajectory. This process supports the exploratory behavior of T cells despite cAMP's traditional role as an immunosuppressive factor.
T lymphocyte migration is an essential step to mounting an efficient immune response. The rapid and random motility of these cells which favors their sentinel role is conditioned by chemokines as well as by the physical environment. Morphological changes, underlaid by dynamic actin cytoskeleton remodeling, are observed throughout migration but especially when the cell modifies its trajectory. However, the signaling cascade regulating the directional changes remains largely unknown. Using dynamic cell imaging, we investigated in this paper the signaling pathways involved in T cell directionality. We monitored cyclic adenosine 3 '-5 ' monosphosphate (cAMP) variation concomitantly with actomyosin distribution upon T lymphocyte migration and highlighted the fact that spontaneous bursts in cAMP starting from the leading edge, are sufficient to promote actomyosin redistribution triggering trajectory modification. Although cAMP is commonly considered as an immunosuppressive factor, our results suggest that, when transient, it rather favors the exploratory behavior of T cells.

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