A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Regulation of CCR7-dependent cell migration through CCR7 homodimer formation
Tekijät: Kobayashi D, Endo M, Ochi H, Hojo H, Miyasaka M, Hayasaka H
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2017
Journal: Scientific Reports
Tietokannassa oleva lehden nimi: SCIENTIFIC REPORTS
Lehden akronyymi: SCI REP-UK
Artikkelin numero: ARTN 8536
Vuosikerta: 7
Sivujen määrä: 14
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-017-09113-4
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/26769066
The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers, we demonstrated a direct contribution of CCR7 homodimerization to CCR7-dependent cell migration and signaling. Induction of stable CCR7 homodimerization resulted in enhanced CCR7-dependent cell migration and CCL19 binding, whereas induction of CXCR4/CCR7 heterodimerization did not. In contrast, dissociation of CCR7 homodimerization by a novel CCR7-derived synthetic peptide attenuated CCR7-dependent cell migration, ligand-dependent CCR7 internalization, ligand-induced actin rearrangement, and Akt and Erk signaling in CCR7-expressing cells. Our study indicates that CCR7 homodimerization critically regulates CCR7 ligand- dependent cell migration and intracellular signaling in multiple cell types.
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