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The absence of LPA1 results in aberrant intestinal epithelial cell migration
Author(s) -
Lee Sei-Jung,
Nusrat Asma,
Chun Jerold,
Yun C. Chris
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1158.4
Subject(s) - lysophosphatidic acid , lamellipodium , cell migration , cortactin , enterocyte , microbiology and biotechnology , rac1 , chemistry , receptor , biology , cell , signal transduction , endocrinology , small intestine , biochemistry , cytoskeleton
Lysophosphatidic acid (LPA) is a potent inducer of epithelial cell migration. The LPA receptor subptype, LPA 1 , is the most abundant LPA receptor in the intestinal tract; however its physiological significance remains elusive. We found that the villous height is shortened in the intestine of LPA 1 ‐null mice ( Lpar1 − / −) compared with wild type (WT) mice and the rate of migration of proliferating enterocytes along the crypt‐villus axis is impaired in Lpar1 −/− mice. Injection of WT mice with LPA 1 /LPA 3 inhibitor Ki16425 decreased cell migration towards the villus tip, whereas oral administration of LPA enhanced cell migration. LPA failed to promote cell migration in Lpar1 −/− mice, suggesting that LPA 1 specifically regulates enterocyte migration in the mouse intestine. We further studied the mechanism of LPA 1 ‐mediated migration in YAMC cells. Overexpression of LPA 1 markedly enhanced lamellipodia formation and cell migration, whereas LPA 2 had a marginal effect. The downstream signaling pathway initiated by LPA 1 for YAMC cell migration involves Gαq specifically activating PLC‐β2, but not other PLC‐β isoforms. PLC‐β2 interacted with GTP‐bound Rac1 to recruit Src and Arp2/3 to the leading edge of lamellipodia, where Src and Arp2/3 interacted with FAK and cortactin, respectively. These results suggest that LPA 1 is the major LPA receptor that regulates migration of proliferating enterocytes in the intestinal tract.