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Ligand-induced changes in integrin expression regulate neuronal adhesion and neurite outgrowth

Nature volume 389, pages 852–856 (1997)Cite this article

Abstract

Receptors of the integrin family are expressed by every cell type and are the primary means by which cells interact with the extracellular matrix. The control of integrin expression affects a wide range of developmental and cellular processes, including the regulation of gene expression, cell adhesion, cell morphogenesis and cell migration1,2,3. Here we show that the concentration of substratum-bound ligand (laminin) post-translationally regulates the amount of receptor (α6β1 integrin) expressed on the surface of sensory neurons. When ligand availability is low, surface amounts of receptor increase, whereas integrin RNA and total integrin protein decrease. Ligand concentration determines surface levels of integrin by altering the rate at which receptor is removed from the cell surface. Furthermore, increased expression of integrin at the cell surface is associated with increased neuronal cell adhesion and neurite outgrowth. These results indicate that integrin regulation maintains neuronal growth-cone motility over a broad range of ligand concentrations, allowing axons to invade different tissues during development and regeneration.

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Figure 1: Characterization of dorsal root ganglion (DRG) neurite outgrowth and integrin expression when cultured on different substratum densities of laminin or on fibronectin.
Figure 2: Analysis of α6 integrin RNA, total α6 integrin protein and surface α6 integrin protein from cells cultured on different concentrations of ligand.
Figure 3: Increased surface expression of integrin receptors increases both cell adhesion and rate of neurite outgrowth.
Figure 4: Summary of the effect of different ligand densities on the surface expression of integrins in growing neurons based on our results and previous work6,16,17,18,28,29.

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Acknowledgements

We thank L. F. Reichardt for integrin antibodies and cDNA, and H. J. Yost and J. F. Challocombe for suggestions on the manuscript. This work was supported by grants from the NIH and the Minnesota Medical Foundation to P.C.L. and the Spinal Cord Research Foundation to M.L.C.

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Authors and Affiliations

  1. Department of Neurobiology and Anatomy, University of Utah, School of Medicine, 50 North Medical Drive, Salt Lake City, 84132, Utah, USA

    M. L. Condic

  2. Department of Cell Biology and Neuroanatomy, 4-135 Jackson Hall, 321 Church Street South-East, University of Minnesota, Minneapolis, 55455, Minnesota, USA

    P. C. Letourneau

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Correspondence to M. L. Condic.

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Condic, M., Letourneau, P. Ligand-induced changes in integrin expression regulate neuronal adhesion and neurite outgrowth. Nature 389, 852–856 (1997). https://doi.org/10.1038/39878

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