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Phosphatidic acid regulates subcellular distribution of RA-GEFs critical for chemokine-dependent migration
Yasuyuki Momoi1, Akihiko Nishikimi1, Guangwei Du2
1Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, Minamiku, Sagamihara, Kanagawa, 252-0337, Japan.
Abstract:
Integrin activation by Rap1-GTP is pivotal for lymphocyte trafficking. In this study, we show the phosphatidic acid (PA)-dependent membrane distribution of RA-GEF-1 and -2 (also known as Rapgef2 and 6), which are guanine nucleotide exchange factors for Rap1, plays important roles in lymphocyte migration. RA-GEF-1 associates with PA through 919-967 aa within CDC25 homology domain, and the deletion of this region of RA-GEF-1 inhibits chemokine-dependent migration. Chemokine stimulation induces temporal production of PA on the plasma membrane, which is not necessary for Rap1 activation, but the translocation of RA-GEFs. Thus, chemokine-dependent generation of PA is critical for lymphocyte migration through membrane localization of RA-GEFs.
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