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PMID: 18477607 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis.

Journal of cell science ·Vol. 121 ·No. 11 ·2008-06-01 ·Pages 1869-75

Matsuki T, Pramatarova A, Howell BW

Abstract

The reelin signaling pathway regulates nervous system function after birth, in addition to its role in regulating neuronal positioning during embryogenesis. The receptor-dependent, reelin-induced tyrosine phosphorylation of the Dab1 docking protein is an established prerequisite for biological responses to this ligand. Here we show that the inactivation of a conditional Dab1 allele reduces process complexity in correctly positioned neurons in the CA1 region of the mouse hippocampus after birth. Reelin stimulation of cultured hippocampal neurons enhances dendritogenesis by approximately twofold and in a manner dependent on Src family kinases. This enhancement is blocked by reducing expression of Crk family proteins, adaptor molecules that interact with Dab1 in a tyrosine phosphorylation-dependent manner. Retrovirally expressed inhibitory RNAs used to reduce Crk and CrkL expression did not block BDNF-enhanced dendritogenesis or influence axonogenesis. Together, this demonstrates that the Crk family proteins are important downstream components of the reelin signaling pathway in the regulation of postnatal hippocampal dendritogenesis.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,metabolism Animals Cell Adhesion Molecules, Neuronal/physiology Cell Differentiation/physiology Cell Shape/physiology Cells, Cultured Dendrites/metabolism,ultrastructure Down-Regulation/genetics Extracellular Matrix Proteins/physiology Hippocampus/embryology,growth & development,metabolism Mice Mice, Knockout Nerve Tissue Proteins/genetics,metabolism,physiology Nuclear Proteins/genetics,metabolism Phosphorylation Proto-Oncogene Proteins c-crk/genetics,metabolism Pyramidal Cells/cytology,metabolism RNA, Small Interfering Reelin Protein Serine Endopeptidases/physiology Signal Transduction/physiology Silver Staining src-Family Kinases/genetics,metabolism
Chemicals
Adaptor Proteins, Signal Transducing CRKL protein Cell Adhesion Molecules, Neuronal Crk protein, mouse Dab1 protein, mouse Extracellular Matrix Proteins Nerve Tissue Proteins Nuclear Proteins Proto-Oncogene Proteins c-crk RNA, Small Interfering Reelin Protein src-Family Kinases Reln protein, mouse Serine Endopeptidases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Matsuki Tohru
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Pramatarova Albéna
Howell Brian W
References (38)
38 references, click to expand
  1. Impaired neuronal positioning and dendritogenesis in the neocortex after cell-autonomous Dab1 suppression.
    J Neurosci. 2006 Feb 8;26(6):1767-75 PMID: 16467525
  2. Nck beta interacts with tyrosine-phosphorylated disabled 1 and redistributes in Reelin-stimulated neurons.
    Mol Cell Biol. 2003 Oct;23(20):7210-21 PMID: 14517291
  3. Interaction of reelin signaling and Lis1 in brain development.
    Nat Genet. 2003 Nov;35(3):270-6 PMID: 14578885
  4. Neuronal polarity in CNS development.
    Genes Dev. 2006 Oct 1;20(19):2639-47 PMID: 17015428
  5. Migration of sympathetic preganglionic neurons in the spinal cord is regulated by Reelin-dependent Dab1 tyrosine phosphorylation and CrkL.
    J Comp Neurol. 2007 Jun 1;502(4):635-43 PMID: 17394141
  6. Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse.
    Dev Biol. 2002 Apr 15;244(2):305-18 PMID: 11944939
  7. Absence of Fyn and Src causes a reeler-like phenotype.
    J Neurosci. 2005 Sep 14;25(37):8578-86 PMID: 16162939
  8. Crk family adaptors-signalling complex formation and biological roles.
    Oncogene. 2001 Oct 1;20(44):6348-71 PMID: 11607838
  9. Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins.
    Biochem Biophys Res Commun. 2004 May 21;318(1):204-12 PMID: 15110774
  10. A protein related to extracellular matrix proteins deleted in the mouse mutant reeler.
    Nature. 1995 Apr 20;374(6524):719-23 PMID: 7715726
  11. The reeler mouse as a model of brain development.
    Adv Anat Embryol Cell Biol. 1998;150:1-106 PMID: 9816727
  12. Phosphatidylinositol 3-kinase interacts with the adaptor protein Dab1 in response to Reelin signaling and is required for normal cortical lamination.
    J Biol Chem. 2003 Oct 3;278(40):38772-9 PMID: 12882964
  13. Mouse disabled 1 regulates the nuclear position of neurons in a Drosophila eye model.
    Mol Cell Biol. 2006 Feb;26(4):1510-7 PMID: 16449660
  14. Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2.
    Cell. 1999 Jun 11;97(6):689-701 PMID: 10380922
  15. Reelin does not directly influence axonal growth.
    J Neurosci. 2001 Dec 1;21(23):RC183 PMID: 11717386
  16. Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development.
    Curr Biol. 2000 Jul 27-Aug 10;10(15):877-85 PMID: 10959835
  17. CrkII regulates focal adhesion kinase activation by making a complex with Crk-associated substrate, p130Cas.
    Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17693-8 PMID: 15598735
  18. Amyloid precursor protein cytoplasmic domain antagonizes reelin neurite outgrowth inhibition of hippocampal neurons.
    Neurobiol Aging. 2008 Apr;29(4):542-53 PMID: 17169463
  19. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference.
    Nat Genet. 2003 Mar;33(3):401-6 PMID: 12590264
  20. Reelin is a ligand for lipoprotein receptors.
    Neuron. 1999 Oct;24(2):471-9 PMID: 10571240
  21. Fyn tyrosine kinase is a critical regulator of disabled-1 during brain development.
    Curr Biol. 2003 Jan 8;13(1):9-17 PMID: 12526739
  22. Cardiovascular and craniofacial defects in Crk-null mice.
    Mol Cell Biol. 2006 Aug;26(16):6272-82 PMID: 16880535
  23. Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome.
    Nat Genet. 2001 Mar;27(3):293-8 PMID: 11242111
  24. Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons.
    Curr Biol. 2004 Apr 6;14(7):606-10 PMID: 15062102
  25. Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation.
    Neuron. 1999 Oct;24(2):481-9 PMID: 10571241
  26. Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway.
    Neuron. 2004 Jan 8;41(1):71-84 PMID: 14715136
  27. Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice.
    Nature. 1997 Oct 16;389(6652):730-3 PMID: 9338784
  28. A novel protein interacts with a clock-related protein, rPer1.
    Brain Res. 2001 Oct 19;916(1-2):1-10 PMID: 11597585
  29. Interaction between Dab1 and CrkII is promoted by Reelin signaling.
    J Cell Sci. 2004 Sep 1;117(Pt 19):4527-36 PMID: 15316068
  30. Hippocampal dendritic arbor growth in vitro: regulation by Reelin-Disabled-1 signaling.
    Brain Res. 2007 Oct 3;1172:1-9 PMID: 17825270
  31. Reelin activates SRC family tyrosine kinases in neurons.
    Curr Biol. 2003 Jan 8;13(1):18-26 PMID: 12526740
  32. Reelin signals through phosphatidylinositol 3-kinase and Akt to control cortical development and through mTor to regulate dendritic growth.
    Mol Cell Biol. 2007 Oct;27(20):7113-24 PMID: 17698586
  33. Reelin-induced tyrosine [corrected] phosphorylation of disabled 1 during neuronal positioning.
    Genes Dev. 1999 Mar 15;13(6):643-8 PMID: 10090720
  34. Neurotrophin-regulated signalling pathways.
    Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545-64 PMID: 16939974
  35. Ligand-activated site-specific recombination in mice.
    Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10887-90 PMID: 8855277
  36. The reeler mouse: anatomy of a mutant.
    Int Rev Neurobiol. 2005;71:383-417 PMID: 16512359
  37. A genetic interaction between the APP and Dab1 genes influences brain development.
    Mol Cell Neurosci. 2008 Jan;37(1):178-86 PMID: 18029196
  38. Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2.
    Neuron. 2005 Aug 18;47(4):567-79 PMID: 16102539
Article Info
Journal
Journal of cell science
Abbr.
J Cell Sci
ISSN
0021-9533
DOI
10.1242/jcs.027334
Published
2008-06-01
Epub
2008-00-13
Pages
1869-75
Language
English
Region
England
NLM ID
0052457
PMCID
PMC2430739
Subset
IM
Grants
Intramural NIH HHS · NIH0010383556 · United States
Intramural NIH HHS · Z01 NS002987-08 · United States
External Links
PubMed source DOI: 10.1242/jcs.027334 PMC Full Text View journal details
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