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

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Waters, C. and Saatian, B. and Akhtar Moughal, N. and Zhao, Y. and Tigyi, G. and Natarajan, V. and Pyne, S. and Pyne, N.J. (2006) Integrin signalling regulates the nuclear localization and function of the lysophosphatidic acid receptor-1 (LPA1) in mammalian cells. Biochemical Journal, 398. pp. 55-62. ISSN 0264-6021 (http://dx.doi.org/10.1042/BJ20060155)

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Abstract

We show that LPA1 (lysophosphatidic acid receptor-1) is constitutively localized in the nucleus of mammalian cells. LPA1 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 LPA1. First, the RGDS peptide, which blocks cell matrix-induced integrin clustering and cytoskeletal rearrangement, reduced the number of cells containing LPA1 in the nucleus. Secondly, a higher proportion of cells contained nuclear LPA1 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 LPA1. The addition of LPA and/or Ki16425 (which binds to LPA1) to isolated nuclei containing LPA1 induced the phosphorylation of several proteins with molecular masses of 34, 32, 14 and 11 kDa. These findings demonstrate that trafficking of LPA1 to the nucleus is influenced by cell-matrix interactions and that nuclear LPA1 may be involved in regulating intranuclear protein phosphorylation and signalling.

ORCID iDs

Waters, C., Saatian, B., Akhtar Moughal, N., Zhao, Y., Tigyi, G., Natarajan, V., Pyne, S. ORCID logoORCID: https://orcid.org/0000-0002-6608-9584 and Pyne, N.J. ORCID logoORCID: https://orcid.org/0000-0002-5657-4578;
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