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Lysophosphatidic Acid Influences the Morphology and Motility of Young, Postmitotic Cortical Neurons

https://doi.org/10.1006/mcne.2002.1123Get rights and content

Abstract

Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that produces process retraction and cell rounding through its cognate receptors in neuroblastoma cell lines. Although the expression profile of LPA receptors in developing brains suggests a role for LPA in central nervous system (CNS) development, how LPA influences the morphology of postmitotic CNS neurons remains to be determined. Here we have investigated the effects of exogenous LPA on the morphology of young, postmitotic neurons in primary culture. When treated with LPA, these neurons responded by not only retracting processes but also producing retraction fiber “caps” characterized by fine actin filaments emanating from a dense core. Retraction fiber caps gradually vanished due to the outward spread of regrowing membranes along the fibers, suggesting a role for caps as scaffolds for regrowth of retracted processes. Furthermore, LPA also affects neuronal migration in vitro and in vivo. Taken together, these results implicate LPA as an extracellular lipid signal affecting process outgrowth and migration of early postmitotic neurons during development.

References (48)

  • W.H. Moolenaar

    Lysophosphatidic acid signalling

    Curr. Opin. Cell Biol.

    (1995)
  • W.H. Moolenaar

    Bioactive lysophospholipids and their G protein-coupled receptors

    Exp. Cell Res.

    (1999)
  • W.H. Moolenaar et al.

    Lysophosphatidic acid: G-protein signalling and cellular responses

    Curr. Opin. Cell Biol.

    (1997)
  • A.J. Ridley et al.

    The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors

    Cell

    (1992)
  • S. Saito

    Effects of lysophosphatidic acid on primary cultured chick neurons

    Neurosci. Lett.

    (1997)
  • C.L. Sayas et al.

    The neurite retraction induced by lysophosphatidic acid increases Alzheimer's disease-like Tau phsophorylation

    J. Biol. Chem.

    (1999)
  • H.J. Song et al.

    Signal transduction underlying growth cone guidance by diffusible factors

    Curr. Opin. Neurobiol.

    (1999)
  • C.A. Walsh et al.

    Potential mechanisms of mutations that affect neuronal migration in man and mouse

    Curr. Opin. Genet. Dev.

    (2000)
  • M. Chrzanowska-Wodnicka et al.

    Rho-stimulated contractility drives the formation of stress fibers and focal adhesions

    J. Cell Biol.

    (1996)
  • J. Chun

    Lysophospholipid receptors: Implications for neural signaling

    Crit. Rev. Neurobiol.

    (1999)
  • J. Chun et al.

    A growing family of receptor genes for lysophosphatidic acid (LPA) and other lyso-phospholipids (LPs)

    Cell Biochem. Biophys.

    (1999)
  • J.J.A. Contos et al.

    Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior

    Proc. Natl. Acad. Sci. USA

    (2000)
  • J.J.A. Contos et al.

    Lysophosphatidic acid receptors

    Mol. Pharmacol.

    (2000)
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    1

    To whom correspondence and reprint requests should be addressed. Fax: 81 11 706 5169. E-mail: [email protected].

    2

    Present address: Department of Anatomy and Neurobiology Washington University School of Medicine, Box 8108, 660 S. Euclid Ave., St. Louis, MO 63110.

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