title: The focal adhesion and nuclear targeting capacity of the LIM-containing lipoma-preferred partner (LPP) protein.
abstract: Targeting of proteins to a particular cellular compartment is a critical determinant for proper functioning. LPP (LIM-containing lipoma-preferred partner) is a LIM domain protein that is localized at sites of cell adhesion and transiently in the nucleus. In various benign and malignant tumors, LPP is present in a mutant form, which permanently localizes the LIM domains in the nucleus. Here, we have investigated which regions in LPP target the protein to its subcellular locations. We found that the LIM domains are the main focal adhesion targeting elements and that the proline-rich region of LPP, which harbors binding sites for alpha-actinin and vasodilator-stimulated phosphoprotein (VASP), has a weak targeting capacity. All of the LIM domains of LPP cooperate in order to provide robust targeting to focal adhesions, and the linker between LIM domains 1 and 2 plays a pivotal role in this targeting. When overexpressed in the cytoplasm of cells, the LIM domains of LPP can deplete endogenous LPP and vinculin from focal adhesions. The proline-rich region of LPP contains targeting sites for focal adhesions and stress fibers that are distinct from the alpha-actinin and VASP binding sites, and the LPP LIM domains are dispensable for targeting LPP to the nucleus. Our studies have defined novel functional domains in the LPP protein.
authors.affiliation: Laboratory for Molecular Oncology, Department of Human Genetics, University of Leuven (K. U. Leuven) & Flanders Interuniversity Institute for Biotechnology (VIB), Herestraat 49, Belgium. marleen.petit@med.kuleuven.ac.be
authors.forename: Marleen M R
authors.initials: MM
authors.lastname: Petit
authors.forename: Sandra M P
authors.initials: SM
authors.lastname: Meulemans
authors.forename: Wim J M
authors.initials: WJ
authors.lastname: Van de Ven
mesh_terms: D016475:3T3 Cells; D000074183:ATPases Associated with Diverse Cellular Activities; D000185:Actinin / Q000737:chemistry; D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D022001:Focal Adhesions; D006023:Glycoproteins; D049452:Green Fluorescent Proteins; D006801:Humans; D060588:LIM Domain Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D008667:Metalloproteins / Q000737:chemistry; D051379:Mice; D008840:Microfilament Proteins; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry; D014162:Transfection; D060589:Zyxin; D001616:beta-Galactosidase / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D060588:LIM Domain Proteins; C103594:LPP protein, human; C491227:Lpp protein, mouse; D008164:Luminescent Proteins; D008667:Metalloproteins; D008840:Microfilament Proteins; C092282:PSMC5 protein, human; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C092842:ZYX protein, human; C498285:Zyx protein, mouse; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein; D000185:Actinin; D049452:Green Fluorescent Proteins; D011392:Proline; D001616:beta-Galactosidase; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities