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PMID: 10884317 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons.

Nakayama AY, Harms MB, Luo L

Abstract

The shape of dendritic trees and the density of dendritic spines can undergo significant changes during the life of a neuron. We report here the function of the small GTPases Rac and Rho in the maintenance of dendritic structures. Maturing pyramidal neurons in rat hippocampal slice culture were biolistically transfected with dominant GTPase mutants. We found that expression of dominant-negative Rac1 results in a progressive elimination of dendritic spines, whereas hyperactivation of RhoA causes a drastic simplification of dendritic branch patterns that is dependent on the activity of a downstream kinase ROCK. Our results suggest that Rac and Rho play distinct functions in regulating dendritic spines and branches and are vital for the maintenance and reorganization of dendritic structures in maturing neurons.

MeSH Terms
Animals Biolistics Cell Differentiation/genetics Dendrites/enzymology,genetics,ultrastructure Gene Expression Genes, Dominant/genetics Genes, Reporter Hippocampus/cytology,enzymology,growth & development In Vitro Techniques Intracellular Signaling Peptides and Proteins Mice Monomeric GTP-Binding Proteins/metabolism Mutagenesis, Site-Directed Phenotype Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism Pyramidal Cells/enzymology,ultrastructure RNA, Messenger/biosynthesis Rats Rats, Long-Evans Signal Transduction/physiology rac1 GTP-Binding Protein/genetics,metabolism rho-Associated Kinases rhoA GTP-Binding Protein/genetics,metabolism
Chemicals
Intracellular Signaling Peptides and Proteins RNA, Messenger Protein Serine-Threonine Kinases rho-Associated Kinases Monomeric GTP-Binding Proteins rac1 GTP-Binding Protein rhoA GTP-Binding Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Nakayama A Y
Department of Biological Sciences and Neurosciences Program, Stanford University, Stanford, California 94305-5020, USA.
Harms M B
Luo L
References (63)
63 references, click to expand
  1. Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42.
    Neuron. 1997 Sep;19(3):625-34 PMID: 9331353
  2. Rho GTPases and signaling networks.
    Genes Dev. 1997 Sep 15;11(18):2295-322 PMID: 9308960
  3. An essential role for Rac in Ras transformation.
    Nature. 1995 Mar 30;374(6521):457-9 PMID: 7700355
  4. Trophic regulation of nerve cell morphology and innervation in the autonomic nervous system.
    Nature. 1988 Nov 10;336(6195):123-8 PMID: 3054564
  5. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis.
    Neuron. 1999 Mar;22(3):451-61 PMID: 10197526
  6. Nerve growth factor enhances dendritic arborization of sympathetic ganglion cells in developing mammals.
    J Neurosci. 1988 Jul;8(7):2628-34 PMID: 3249248
  7. The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity.
    Nature. 1998 Sep 10;395(6698):194-8 PMID: 9744280
  8. A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons.
    Neuron. 2000 May;26(2):431-41 PMID: 10839361
  9. p160ROCK, a Rho-associated coiled-coil forming protein kinase, works downstream of Rho and induces focal adhesions.
    FEBS Lett. 1997 Mar 10;404(2-3):118-24 PMID: 9119047
  10. Osteogenic protein-1 induces dendritic growth in rat sympathetic neurons.
    Neuron. 1995 Sep;15(3):597-605 PMID: 7546739
  11. Comparison of hippocampal dendritic spines in culture and in brain.
    J Neurosci. 1998 Jul 15;18(14):5294-300 PMID: 9651212
  12. Dendritic spine changes associated with hippocampal long-term synaptic plasticity.
    Nature. 1999 May 6;399(6731):66-70 PMID: 10331391
  13. A strategy for the analysis of gene expression during neural development.
    Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9970-4 PMID: 7937928
  14. A role for Rho in Ras transformation.
    Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11781-5 PMID: 8524848
  15. Dynamic changes in the dendritic geometry of individual neurons visualized over periods of up to three months in the superior cervical ganglion of living mice.
    J Neurosci. 1986 Apr;6(4):1051-60 PMID: 3701409
  16. Destabilization of cortical dendrites and spines by BDNF.
    Neuron. 1999 Jun;23(2):353-64 PMID: 10399940
  17. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)
    Science. 1996 Jul 12;273(5272):245-8 PMID: 8662509
  18. The guanine nucleotide exchange factor Tiam1 affects neuronal morphology; opposing roles for the small GTPases Rac and Rho.
    J Cell Biol. 1997 Nov 3;139(3):797-807 PMID: 9348295
  19. Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth.
    Neuron. 1997 May;18(5):767-78 PMID: 9182801
  20. Axonal atrophy: the retraction reaction.
    Curr Opin Neurobiol. 1999 Jun;9(3):364-70 PMID: 10395581
  21. Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation.
    Nature. 1998 Apr 30;392(6679):923-6 PMID: 9582072
  22. Growth cone guidance: first steps towards a deeper understanding.
    Annu Rev Neurosci. 1999;22:351-88 PMID: 10202543
  23. PAK promotes morphological changes by acting upstream of Rac.
    EMBO J. 1998 Aug 3;17(15):4328-39 PMID: 9687501
  24. The small GTPase Rho: cellular functions and signal transduction.
    J Biochem. 1996 Aug;120(2):215-28 PMID: 8889802
  25. Leukemia inhibitory factor and ciliary neurotrophic factor cause dendritic retraction in cultured rat sympathetic neurons.
    J Neurosci. 1999 Mar 15;19(6):2113-21 PMID: 10066264
  26. Molecular determinants for subcellular localization of PSD-95 with an interacting K+ channel.
    Neuron. 1999 May;23(1):149-57 PMID: 10402201
  27. Neuronal transfection in brain slices using particle-mediated gene transfer.
    Neuron. 1994 Dec;13(6):1263-8 PMID: 7993619
  28. Breakthroughs in molecular and cellular mechanisms underlying X-linked mental retardation.
    Hum Mol Genet. 1999;8(10):1833-8 PMID: 10469834
  29. PAK3 mutation in nonsyndromic X-linked mental retardation.
    Nat Genet. 1998 Sep;20(1):25-30 PMID: 9731525
  30. Imaging cells in the developing nervous system with retrovirus expressing modified green fluorescent protein.
    Exp Neurol. 1999 Apr;156(2):394-406 PMID: 10328944
  31. Neurotrophins regulate dendritic growth in developing visual cortex.
    Neuron. 1995 Oct;15(4):791-803 PMID: 7576629
  32. LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite.
    Nature. 1999 Nov 25;402(6760):421-5 PMID: 10586883
  33. A simple method for organotypic cultures of nervous tissue.
    J Neurosci Methods. 1991 Apr;37(2):173-82 PMID: 1715499
  34. Role of citron kinase as a target of the small GTPase Rho in cytokinesis.
    Nature. 1998 Jul 30;394(6692):491-4 PMID: 9697773
  35. Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho.
    J Cell Biol. 1994 Aug;126(3):801-10 PMID: 8045941
  36. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
    Cell. 1992 Aug 7;70(3):401-10 PMID: 1643658
  37. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity.
    Science. 1999 Mar 19;283(5409):1923-7 PMID: 10082466
  38. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension.
    Nature. 1997 Oct 30;389(6654):990-4 PMID: 9353125
  39. Structure, sequence, and polymorphism of the Lyt-2 T cell differentiation antigen gene.
    J Immunol. 1986 Aug 1;137(3):1037-43 PMID: 3487583
  40. The neuronal architecture of Xenopus retinal ganglion cells is sculpted by rho-family GTPases in vivo.
    J Neurosci. 1999 Oct 1;19(19):8454-63 PMID: 10493746
  41. Promotion of dendritic growth by CPG15, an activity-induced signaling molecule.
    Science. 1998 Sep 18;281(5384):1863-6 PMID: 9743502
  42. Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK/SAPK MAP kinase cascade.
    Cell. 1996 Nov 1;87(3):519-29 PMID: 8898204
  43. Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid.
    Mol Cell Biol. 1997 Mar;17(3):1201-11 PMID: 9032247
  44. Spine loss in experimental epilepsy: quantitative light and electron microscopic analysis of intracellularly stained CA3 pyramidal cells in hippocampal slice cultures.
    Neuroscience. 1996 Jan;70(1):31-45 PMID: 8848134
  45. Neurotrophin receptor mRNA expression defines distinct populations of neurons in rat dorsal root ganglia.
    J Comp Neurol. 1995 Jan 16;351(3):329-38 PMID: 7706545
  46. Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function.
    Annu Rev Neurosci. 1994;17:341-71 PMID: 8210179
  47. Molecular dissection of the Rho-associated protein kinase (p160ROCK)-regulated neurite remodeling in neuroblastoma N1E-115 cells.
    J Cell Biol. 1998 Jun 29;141(7):1625-36 PMID: 9647654
  48. Rapid actin-based plasticity in dendritic spines.
    Neuron. 1998 May;20(5):847-54 PMID: 9620690
  49. Dendritic integration in mammalian neurons, a century after Cajal.
    Neuron. 1996 Apr;16(4):701-16 PMID: 8607989
  50. Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat.
    J Comp Neurol. 1993 Oct 8;336(2):293-306 PMID: 8245220
  51. Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines.
    Nature. 1996 Feb 29;379(6568):837-40 PMID: 8587609
  52. Changes in the dendritic branching of adult mammalian neurones revealed by repeated imaging in situ.
    Nature. 1985 May 30-Jun 5;315(6018):404-6 PMID: 4000267
  53. Rho GTPases regulate distinct aspects of dendritic arbor growth in Xenopus central neurons in vivo.
    Nat Neurosci. 2000 Mar;3(3):217-25 PMID: 10700252
  54. A brain serine/threonine protein kinase activated by Cdc42 and Rac1.
    Nature. 1994 Jan 6;367(6458):40-6 PMID: 8107774
  55. RAC regulation of actin polymerization and proliferation by a pathway distinct from Jun kinase.
    Science. 1996 Nov 22;274(5291):1374-6 PMID: 8910277
  56. Regulation of the POU domain gene SCIP during cerebral cortical development.
    J Neurosci. 1994 Feb;14(2):472-85 PMID: 7905511
  57. Structure, development, and plasticity of dendritic spines.
    Curr Opin Neurobiol. 1999 Jun;9(3):343-8 PMID: 10395574
  58. The dynamics of dendritic structure in developing hippocampal slices.
    J Neurosci. 1996 May 1;16(9):2983-94 PMID: 8622128
  59. Essential roles of Drosophila RhoA in the regulation of neuroblast proliferation and dendritic but not axonal morphogenesis.
    Neuron. 2000 Feb;25(2):307-16 PMID: 10719887
  60. Small GTP-binding proteins and the regulation of the actin cytoskeleton.
    Annu Rev Cell Biol. 1994;10:31-54 PMID: 7888179
  61. Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth.
    Neuron. 1999 Nov;24(3):585-93 PMID: 10595511
  62. Dendritic organization in the neurons of the visual and motor cortices of the cat.
    J Anat. 1953 Oct;87(4):387-406 PMID: 13117757
  63. Rho family GTP-binding proteins in growth cone signalling.
    Curr Opin Neurobiol. 1997 Feb;7(1):81-6 PMID: 9039798
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
2000-07-15
Pages
5329-38
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772334
Subset
IM
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