Integrin signalling regulates the nuclear localization and function of the lysophosphatidic acid receptor-1 (LPA1) in mammalian cells.
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.
Waters
Catherine M
CM
Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor St, Glasgow, G4 0NR, UK.
Saatian
Bahman
B
Moughal
Noreen A
NA
Zhao
Yutong
Y
Tigyi
Gabor
G
Natarajan
Viswanathan
V
Pyne
Susan
S
Pyne
Nigel J
NJ
D000818:Animals; D016466:CHO Cells; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007555:Isoxazoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D016716:PC12 Cells; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D015398:Signal Transduction; D054460:rho-Associated Kinases
C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D007555:Isoxazoles; D008246:Lysophospholipids; D011422:Propionates; D049368:Receptors, Lysophosphatidic Acid; D037342:Pertussis Toxin; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C032881:lysophosphatidic acid