Integrin signalling regulates the nuclear localization and function of the lysophosphatidic acid receptor-1 (LPA 1}) in mammalian cells

Catherine M Waters , Bahman Saatian , Noreen A Moughal , Yutong Zhao , Gabor Tigyi , Viswanathan Natarajan , Susan Pyne , Nigel J Pyne (1)

1 Department of Physiology and Pharmacology

We show here that the lysophosphatidic acid receptor-1 (LPA 1}) is constitutively localised in the nucleus of mammalian cells. LPA 1} also traffics from cell membranes to the nucleus in response to LPA. Several lines of evidence also suggest an important role for cell-matrix interaction in regulating the constitutive nuclear localisation of LPA 1}. First, RGDS, which blocks cell matrix-induced integrin clustering and cytoskeletal rearrangement, reduced the number of cells containing LPA 1} in the nucleus. Second, a higher proportion of cells contained nuclear LPA 1} when adhesion on fibronectin coated glass was compared with adherence to polylysine coated glass. Third, pre-treatment of cells with the Rho kinase inhibitor (Y27632) or the MLCK inhibitor (ML9) reduced the number of cells containing nuclear LPA 1}. The addition of LPA and/or Ki16425 (which binds to LPA 1}) to isolated nuclei containing LPA 1} induced the phosphorylation of several proteins with molecular masses of 34, 32, 14 and 11kDa. These findings demonstrate that trafficking of LPA 1} to the nucleus is influenced by cell-matrix interactions and that nuclear LPA 1} may be involved in regulating intranuclear protein phosphorylation and signalling.

Mots clés: Life Sciences

Catherine M Waters, Bahman Saatian, Noreen A Moughal, Yutong Zhao, Gabor Tigyi, et al.. Integrin signalling regulates the nuclear localization and function of the lysophosphatidic acid receptor-1 (LPA 1}) in mammalian cells. Biochemical Journal, 2006, 398 (1), pp.55-62. ⟨10.1042/BJ20060155⟩. ⟨hal-00478521⟩