Integrin signalling regulates the nuclear localization and function of the lysophosphatidic acid receptor-1 (LPA1) in mammalian cells

We show that LPA(1) (lysophosphatidic acid receptor-1) is constitutively localized in the nucleus of mammalian cells. LPA(1) also traffics from cell membranes to the nucleus in response to LPA (lysophosphatidic acid). Several lines of evidence suggest an important role for cell-matrix interaction in regulating the constitutive nuclear localization of LPA(1). First, the RGDS peptide, which blocks cell matrix-induced integrin clustering and cytoskeletal rearrangement, reduced the number of cells containing LPA(1) in the nucleus. Secondly, a higher proportion of cells contained nuclear LPA(1) when adhesion on fibronectin-coated glass was compared with adherence to polylysine-coated glass. Thirdly, pre-treatment of cells with the Rho kinase inhibitor (Y27632) or the myosin light chain kinase inhibitor (ML9) reduced the number of cells containing nuclear LPA(1). The addition of LPA(1) 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 11 kDa. 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.