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The fibroblast growth factor receptor substrate 3 adapter is a developmentally regulated microtubule-associated protein expressed in migrating and differentiated neurons

  1. Todd Hryciw1,
  2. James I. S. MacDonald1,
  3. Renée Phillips1,2,
  4. Claudia Seah1,
  5. Stephen Pasternak1,4,
  6. Susan O. Meakin1,2,3

Article first published online: 24 NOV 2009

DOI: 10.1111/j.1471-4159.2009.06503.x

Issue

Journal of Neurochemistry

Journal of Neurochemistry

Volume 112, Issue 4, pages 924–939, February 2010

Additional Information

How to Cite

Hryciw, T., MacDonald, J. I. S., Phillips, R., Seah, C., Pasternak, S. and Meakin, S. O. (2010), The fibroblast growth factor receptor substrate 3 adapter is a developmentally regulated microtubule-associated protein expressed in migrating and differentiated neurons. Journal of Neurochemistry, 112: 924–939. doi: 10.1111/j.1471-4159.2009.06503.x

Author Information

  1. 1

    Molecular Brain Research Group, Robarts Research Institute, London, Ontario, Canada

  2. 2

    Graduate Program in Neuroscience, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada

  3. 3

    Department of Clinical Neurological Sciences, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada

  4. 4

    Department of Biochemistry, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada

*Address correspondence and reprint requests to Susan Meakin, Molecular Brain Research Group, Laboratory of Neural Signaling, Robarts Research Institute, 100 Perth Drive, London, ON, Canada N6A 5K8. E-mail: smeakin@robarts.ca

Publication History

  1. Issue published online: 20 JAN 2010
  2. Article first published online: 24 NOV 2009
  3. Received September 15, 2009; revised manuscript received November 16, 2009; accepted November 17, 2009.

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Keywords:

  • cortical neurogenesis;
  • FGF receptor signaling;
  • Frs3/Frs2β;
  • lipid rafts;
  • microtubules

J. Neurochem. (2009) 112, 924–939.

Abstract

Fibroblast growth factor (FGF) mediated signaling is essential to many aspects of neural development. Activated FGF receptors signal primarily through the FGF receptor substrate (Frs) adapters, which include Frs2/Frs2α and Frs3/Frs2β. While some studies suggest that Frs3 can compensate for the loss of Frs2 in transfected cells, the lack of an effective Frs3 specific antibody has prevented efforts to determine the role(s) of the endogenous protein. To this end, we have generated a Frs3 specific antibody and have characterized the pattern of Frs3 expression in the developing nervous system, its subcellular localization as well as its biochemical properties. We demonstrate that Frs3 is expressed at low levels in the ventricular zone of developing cortex, between E12 and E15, and it co-localizes with nestin and acetylated α-tubulin in radial processes in the ventricular/subventricular zones as well as with βIII tubulin in differentiated cortical neurons. Subcellular fractionation studies demonstrate that endogenous Frs3 is both soluble and plasma membrane associated while Frs3 expressed in 293T cells associates exclusively with lipid rafts. Lastly, we demonstrate that neuronal Frs3 binds microtubules comparable to the microtubule-associated protein, MAP2, while Frs2 does not. Collectively, these data suggest that neuronal Frs3 functions as a novel microtubule binding protein and they provide the first biochemical evidence that neuronal Frs3 is functionally distinct from Frs2/Frs2α.

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