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PMID: 12707308 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Control of axon elongation via an SDF-1alpha/Rho/mDia pathway in cultured cerebellar granule neurons.

The Journal of cell biology ·Vol. 161 ·No. 2 ·2003-04-28 ·Pages 381-91

Arakawa Y, Bito H, Furuyashiki T, Tsuji T, Takemoto-Kimura S, Kimura K, Nozaki K, Hashimoto N, Narumiya S

Abstract

Rho-GTPase has been implicated in axon outgrowth. However, not all of the critical steps controlled by Rho have been well characterized. Using cultured cerebellar granule neurons, we show here that stromal cell-derived factor (SDF)-1alpha, a neural chemokine, is a physiological ligand that can turn on two distinct Rho-dependent pathways with opposite consequences. A low concentration of the ligand stimulated a Rho-dependent pathway that mediated facilitation of axon elongation. In contrast, Rho/ROCK activation achieved by a higher concentration of SDF-1alpha caused repression of axon formation and induced no more increase in axon length. However, even at this higher concentration a Rho-dependent axon elongating activity could be recovered upon removal of ROCK activity using Y-27632. SDF-1alpha-induced axon elongating activity under ROCK inhibition was replicated by the dominant-active form of the mammalian homologue of the Drosophila gene Diaphanous (mDia)1 and counteracted by its dominant-negative form. Furthermore, RNAi knockdown of mDia1 abolished SDF-1alpha-induced axon elongation. Together, our results support a critical role for an SDF-1alpha/Rho/mDia1 pathway in mediating axon elongation.

MeSH Terms
Actins/metabolism Animals Carrier Proteins/genetics,metabolism Cell Differentiation/drug effects,genetics Cells, Cultured Cerebellar Cortex/cytology,growth & development,metabolism Chemokine CXCL12 Chemokines, CXC/metabolism,pharmacology Dose-Response Relationship, Drug Enzyme Inhibitors/pharmacology Formins Gene Expression Regulation, Developmental/drug effects,genetics Growth Cones/drug effects,metabolism,ultrastructure Intracellular Signaling Peptides and Proteins Mice Mutation Protein Serine-Threonine Kinases/drug effects,metabolism RNA Interference/physiology Signal Transduction/drug effects,genetics rac GTP-Binding Proteins/drug effects,metabolism rho GTP-Binding Proteins/drug effects,metabolism rho-Associated Kinases
Chemicals
Actins Carrier Proteins Chemokine CXCL12 Chemokines, CXC Cxcl12 protein, mouse Diap1 protein, mouse Enzyme Inhibitors Formins Intracellular Signaling Peptides and Proteins Protein Serine-Threonine Kinases rho-Associated Kinases rac GTP-Binding Proteins rho GTP-Binding Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Arakawa Yoshiki
Dept. of Pharmacology, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606-8315, Japan.
Bito Haruhiko
Furuyashiki Tomoyuki
Tsuji Takahiro
Takemoto-Kimura Sayaka
Kimura Kazuhiro
Nozaki Kazuhiko
Hashimoto Nobuo
Narumiya Shuh
References (68)
68 references, click to expand
  1. Rho GTPases and the actin cytoskeleton.
    Science. 1998 Jan 23;279(5350):509-14 PMID: 9438836
  2. Axon guidance: GTPases help axons reach their targets.
    Curr Biol. 1998 Jan 29;8(3):R80-2 PMID: 9443904
  3. Drosophila Rac1 controls motor axon guidance.
    Development. 1998 Feb;125(3):453-61 PMID: 9425140
  4. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract.
    Nature. 1998 Jun 11;393(6685):591-4 PMID: 9634237
  5. Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth.
    Neuron. 1999 Nov;24(3):585-93 PMID: 10595511
  6. Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases.
    Mol Pharmacol. 2000 May;57(5):976-83 PMID: 10779382
  7. Rho small G-protein-dependent binding of mDia to an Src homology 3 domain-containing IRSp53/BAIAP2.
    Biochem Biophys Res Commun. 2000 May 19;271(3):626-9 PMID: 10814512
  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. Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila.
    Cell. 2000 Apr 28;101(3):283-94 PMID: 10847683
  10. Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth.
    Neuron. 2000 Jun;26(3):633-46 PMID: 10896159
  11. Discoidin domain receptor 1 functions in axon extension of cerebellar granule neurons.
    Genes Dev. 2000 Sep 1;14(17):2216-28 PMID: 10970885
  12. Dynamic localization and function of Bni1p at the sites of directed growth in Saccharomyces cerevisiae.
    Mol Cell Biol. 2001 Feb;21(3):827-39 PMID: 11154270
  13. Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1.
    Nat Cell Biol. 2001 Jan;3(1):8-14 PMID: 11146620
  14. Rho GTPases in growth cone guidance.
    Curr Opin Neurobiol. 2001 Feb;11(1):103-10 PMID: 11179879
  15. Rho GTPases in neuronal morphogenesis.
    Nat Rev Neurosci. 2000 Dec;1(3):173-80 PMID: 11257905
  16. Developmental pattern of expression of the alpha chemokine stromal cell-derived factor 1 in the rat central nervous system.
    Eur J Neurosci. 2001 Mar;13(5):845-56 PMID: 11264658
  17. Plexin-B semaphorin receptors interact directly with active Rac and regulate the actin cytoskeleton by activating Rho.
    Curr Biol. 2001 Mar 6;11(5):339-44 PMID: 11267870
  18. Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction.
    Cell. 2001 Apr 6;105(1):69-79 PMID: 11301003
  19. EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin.
    Cell. 2001 Apr 20;105(2):233-44 PMID: 11336673
  20. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells.
    Nature. 2001 May 24;411(6836):494-8 PMID: 11373684
  21. mDia mediates Rho-regulated formation and orientation of stable microtubules.
    Nat Cell Biol. 2001 Aug;3(8):723-9 PMID: 11483957
  22. SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells.
    Development. 2001 Jun;128(11):1971-81 PMID: 11493520
  23. Neurotrophins: roles in neuronal development and function.
    Annu Rev Neurosci. 2001;24:677-736 PMID: 11520916
  24. Semaphorin-mediated axonal guidance via Rho-related G proteins.
    Curr Opin Cell Biol. 2001 Oct;13(5):619-26 PMID: 11544032
  25. Regulation of neurotrophin-induced axonal responses via Rho GTPases.
    J Comp Neurol. 2001 Oct 1;438(4):377-87 PMID: 11559894
  26. mDia-interacting protein acts downstream of Rho-mDia and modifies Src activation and stress fiber formation.
    J Biol Chem. 2001 Oct 19;276(42):39290-4 PMID: 11509578
  27. Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway.
    Cell. 2001 Oct 19;107(2):209-21 PMID: 11672528
  28. Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum.
    Development. 2001 Aug;128(16):3133-44 PMID: 11688562
  29. A novel Dbl family RhoGEF promotes Rho-dependent axon attraction to the central nervous system midline in Drosophila and overcomes Robo repulsion.
    J Cell Biol. 2001 Dec 24;155(7):1117-22 PMID: 11756465
  30. Rac GTPases control axon growth, guidance and branching.
    Nature. 2002 Mar 28;416(6879):442-7 PMID: 11919635
  31. The role of Rho GTPases and associated kinases in regulating neurite outgrowth.
    Int J Biochem Cell Biol. 2002 Jul;34(7):731-45 PMID: 11950591
  32. Rac1 and Cdc42 but not RhoA or Rho kinase activities are required for neurite outgrowth induced by the Netrin-1 receptor DCC (deleted in colorectal cancer) in N1E-115 neuroblastoma cells.
    J Biol Chem. 2002 Apr 26;277(17):15207-14 PMID: 11844789
  33. Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor.
    Proc Natl Acad Sci U S A. 2002 May 14;99(10):7090-5 PMID: 11983855
  34. ROCK and mDia1 antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts.
    J Cell Biol. 2002 May 27;157(5):819-30 PMID: 12021256
  35. Intrinsic program for migration of cerebellar granule cells in vitro.
    J Neurosci. 2002 Jul 15;22(14):5966-81 PMID: 12122059
  36. Rac1-mediated endocytosis during ephrin-A2- and semaphorin 3A-induced growth cone collapse.
    J Neurosci. 2002 Jul 15;22(14):6019-28 PMID: 12122063
  37. Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology.
    Neuron. 2002 Jul 3;35(1):51-63 PMID: 12123608
  38. Role of formins in actin assembly: nucleation and barbed-end association.
    Science. 2002 Jul 26;297(5581):612-5 PMID: 12052901
  39. An actin nucleation mechanism mediated by Bni1 and profilin.
    Nat Cell Biol. 2002 Aug;4(8):626-31 PMID: 12134165
  40. Role of the chemokine SDF-1 as the meningeal attractant for embryonic cerebellar neurons.
    Nat Neurosci. 2002 Aug;5(8):719-20 PMID: 12080344
  41. Characterization of new cell permeable C3-like proteins that inactivate Rho and stimulate neurite outgrowth on inhibitory substrates.
    J Biol Chem. 2002 Sep 6;277(36):32820-9 PMID: 12091381
  42. Nerve growth factor signals through TrkA, phosphatidylinositol 3-kinase, and Rac1 to inactivate RhoA during the initiation of neuronal differentiation of PC12 cells.
    J Biol Chem. 2002 Sep 27;277(39):35840-6 PMID: 12133829
  43. Developmental mechanisms that generate precise patterns of neuronal connectivity.
    Cell. 1993 Jan;72 Suppl:77-98 PMID: 8428376
  44. Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins.
    Science. 1993 Jul 30;261(5121):600-3 PMID: 8342023
  45. Molecular cloning and structure of a pre-B-cell growth-stimulating factor.
    Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2305-9 PMID: 8134392
  46. Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion.
    Genes Dev. 1994 Aug 1;8(15):1787-802 PMID: 7958857
  47. Making the connection: cytoskeletal rearrangements during growth cone guidance.
    Cell. 1995 Oct 20;83(2):171-6 PMID: 7585934
  48. Preparation of native and recombinant Clostridium botulinum C3 ADP-ribosyltransferase and identification of Rho proteins by ADP-ribosylation.
    Methods Enzymol. 1995;256:196-206 PMID: 7476433
  49. 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
  50. The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation.
    Genes Dev. 1996 Apr 1;10(7):816-25 PMID: 8846918
  51. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1.
    Nature. 1996 Aug 15;382(6592):635-8 PMID: 8757135
  52. The molecular biology of axon guidance.
    Science. 1996 Nov 15;274(5290):1123-33 PMID: 8895455
  53. CREB phosphorylation and dephosphorylation: a Ca(2+)- and stimulus duration-dependent switch for hippocampal gene expression.
    Cell. 1996 Dec 27;87(7):1203-14 PMID: 8980227
  54. Development of polarity in cerebellar granule neurons.
    J Neurobiol. 1997 Feb;32(2):223-36 PMID: 9032664
  55. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development.
    Nature. 1998 Jun 11;393(6685):595-9 PMID: 9634238
  56. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice.
    Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9448-53 PMID: 9689100
  57. The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity.
    Nature. 1998 Sep 10;395(6698):194-8 PMID: 9744280
  58. Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton.
    EMBO J. 1999 Feb 1;18(3):578-85 PMID: 9927417
  59. Cooperation between mDia1 and ROCK in Rho-induced actin reorganization.
    Nat Cell Biol. 1999 Jul;1(3):136-43 PMID: 10559899
  60. Central nervous system neuronal migration.
    Annu Rev Neurosci. 1999;22:511-39 PMID: 10202547
  61. The middle and the end: slit brings guidance and branching together in axon pathway selection.
    Neuron. 1999 Apr;22(4):649-52 PMID: 10230784
  62. Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila.
    Cell. 1999 Jun 25;97(7):853-63 PMID: 10399914
  63. Different roles for RhoA during neurite initiation, elongation, and regeneration in PC12 cells.
    J Neurochem. 1999 Sep;73(3):949-60 PMID: 10461884
  64. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin.
    EMBO J. 1997 Jun 2;16(11):3044-56 PMID: 9214622
  65. Rac1 mediates collapsin-1-induced growth cone collapse.
    J Neurosci. 1997 Aug 15;17(16):6256-63 PMID: 9236236
  66. Rho effectors and reorganization of actin cytoskeleton.
    FEBS Lett. 1997 Jun 23;410(1):68-72 PMID: 9247125
  67. Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42.
    Neuron. 1997 Sep;19(3):625-34 PMID: 9331353
  68. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension.
    Nature. 1997 Oct 30;389(6654):990-4 PMID: 9353125
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200210149
Published
2003-04-28
Epub
2003-00-21
Pages
381-91
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172896
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200210149 PMC Full Text View journal details
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