Nucleolar localization signals of LIM kinase 2 function as a cell-penetrating peptide

Protein Pept Lett. 2010 Dec;17(12):1480-8. doi: 10.2174/0929866511009011480.

Abstract

LIM Kinase 2 (LIMK2) is a LIM domain-containing protein kinase which regulates actin polymerization thorough phosphorylation of the actin depolymerizing factor cofilin. It is also known to function as a shuttle between the cytoplasm and nucleus in endothelial cells. A basic amino acid-rich motif in LIMK2 was previously identified to be responsible for this shuttling function, as a nucleolar localization signal (NoLS). Here it is shown that this nucleolar localization signal sequence also has the characteristic function of a cell-penetrating peptide (CPP). We synthesized LIMK2 NoLS-conjugated peptides and a protein and analyzed their cell-penetrating abilities in various types of cells. The BC-box motif of the Von Hippel-Lindau (VHL) protein was used for the peptide. This motif previously has been reported to be involved in the neural differentiation of bone marrow stromal cells and skin-derived precursor cells. Green fluorescence protein (GFP) was used as a large biologically active biomolecule for the protein. The LIMK2 NoLS-conjugated peptides and protein translocated across the cell membranes of fibroblast cells, neural stem cells, and even iPS cells. These results suggest that LIMK2 NoLS acts as a cell-penetrating peptide and its cell-penetrating ability is not restricted by cell type. Moreover, from an in vivo assay using a mouse brain, it was confirmed that NoLS has potential for transporting biomolecules across the blood-brain barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood-Brain Barrier / metabolism
  • Cell Nucleolus / metabolism*
  • Cell-Penetrating Peptides / chemistry*
  • Cells, Cultured
  • Fibroblasts / metabolism
  • Humans
  • Infant, Newborn
  • Lim Kinases / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neural Stem Cells / metabolism
  • Nuclear Localization Signals / chemistry*
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism

Substances

  • Cell-Penetrating Peptides
  • Nuclear Localization Signals
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Lim Kinases