Nuclear-cytoplasmic shuttling of the focal contact protein, zyxin: a potential mechanism for communication between sites of cell adhesion and the nucleus.
Integrin-dependent cell adhesion to specific extracellular matrix molecules has been demonstrated to trigger dramatic changes in gene expression that can affect cell fate. However, little is understood about the molecular mechanism by which events at sites of cell- substratum adhesion are communicated to the cell interior to regulate the transcriptional apparatus. By analogy to classical mechanisms of cell surface receptor function, it seems likely that some components of the integrin-activated signal transduction machinery will be colocalized with cell adhesion molecules. Zyxin is a low abundance phosphoprotein that accumulates with integrins at sites of cell-substratum attachment. Here we show that zyxin exhibits a functional nuclear export signal that is required to keep zyxin concentrated in the cytoplasm and is sufficient to direct nuclear proteins to the cytosol. Furthermore, we demonstrate that native zyxin shuttles between the nucleus and sites of cell adhesion in fibroblasts and is thus an excellent candidate for relaying information between these two compartments.
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Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
Beckerle
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D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology*; D002645:Chickens; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003593:Cytoplasm / Q000502:physiology; D005347:Fibroblasts; D005982:Glutathione Transferase; D007930:Leucine; D008667:Metalloproteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D014158:Transcription, Genetic; D016335:Zinc Fingers; D060589:Zyxin
D030161:Avian Proteins; D015815:Cell Adhesion Molecules; D008667:Metalloproteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D060589:Zyxin; D005982:Glutathione Transferase; D007930:Leucine