Home LiteratureArticle Details
PMID: 11739584 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Axon branching requires interactions between dynamic microtubules and actin filaments.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 24 ·2001-12-15 ·Pages 9757-69

Dent EW, Kalil K

Abstract

Cortical neurons innervate many of their targets by collateral axon branching, which requires local reorganization of the cytoskeleton. We coinjected cortical neurons with fluorescently labeled tubulin and phalloidin and used fluorescence time-lapse imaging to analyze interactions between microtubules and actin filaments (F-actin) in cortical growth cones and axons undergoing branching. In growth cones and at axon branch points, splaying of looped or bundled microtubules is accompanied by focal accumulation of F-actin. Dynamic microtubules colocalize with F-actin in transition regions of growth cones and at axon branch points. In contrast, F-actin is excluded from the central region of the growth cone and the axon shaft, which contains stable microtubules. Interactions between dynamic microtubules and dynamic actin filaments involve their coordinated polymerization and depolymerization. Application of drugs that attenuate either microtubule or F-actin dynamics also inhibits polymerization of the other cytoskeletal element. Importantly, inhibition of microtubule or F-actin dynamics prevents axon branching but not axon elongation. However, these treatments do cause undirected axon outgrowth. These results suggest that interactions between dynamic microtubules and actin filaments are required for axon branching and directed axon outgrowth.

MeSH Terms
Actin Cytoskeleton/drug effects,metabolism Actins/metabolism Animals Axons/drug effects,physiology Cattle Cells, Cultured Cerebral Cortex/cytology,drug effects,metabolism Cricetinae Growth Cones/drug effects,metabolism Mesocricetus Microinjections Microtubules/drug effects,metabolism Neurons/cytology,drug effects,metabolism Phalloidine/pharmacology Protein Binding/drug effects Tubulin/pharmacology
Chemicals
Actins Tubulin Phalloidine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dent E W
Neuroscience Training Program and Department of Anatomy, University of Wisconsin, Madison, Wisconsin 53706, USA.
Kalil K
References (66)
66 references, click to expand
  1. The Ig superfamily cell adhesion molecule, apCAM, mediates growth cone steering by substrate-cytoskeletal coupling.
    J Cell Biol. 1998 Apr 6;141(1):227-40 PMID: 9531561
  2. Cdc42 stimulates neurite outgrowth and formation of growth cone filopodia and lamellipodia.
    J Neurobiol. 2000 Jun 15;43(4):352-64 PMID: 10861561
  3. Individual microtubules in the axon consist of domains that differ in both composition and stability.
    J Cell Biol. 1990 Aug;111(2):495-509 PMID: 2199458
  4. A high-resolution multimode digital microscope system.
    Methods Cell Biol. 1998;56:185-215 PMID: 9500139
  5. Dynamic microtubule ends are required for growth cone turning to avoid an inhibitory guidance cue.
    J Neurosci. 1997 May 1;17(9):3085-95 PMID: 9096143
  6. New anti-actin drugs in the study of the organization and function of the actin cytoskeleton.
    Microsc Res Tech. 1999 Oct 1;47(1):18-37 PMID: 10506759
  7. Cytoskeletal remodeling during growth cone-target interactions.
    J Cell Biol. 1993 Jun;121(6):1369-83 PMID: 8509456
  8. Microtubule behavior in the growth cones of living neurons during axon elongation.
    J Cell Biol. 1991 Oct;115(2):345-63 PMID: 1918145
  9. Nerve growth cone lamellipodia contain two populations of actin filaments that differ in organization and polarity.
    J Cell Biol. 1992 Dec;119(5):1219-43 PMID: 1447299
  10. Microtubule assembly and turnover in growing axons.
    J Neurosci. 1996 Jan 15;16(2):531-44 PMID: 8551337
  11. Cytoskeletal events in growth cone steering.
    Curr Opin Neurobiol. 1994 Feb;4(1):43-8 PMID: 8173324
  12. The organization of myosin and actin in rapid frozen nerve growth cones.
    J Cell Biol. 1989 Jan;108(1):95-109 PMID: 2642912
  13. Nanomolar concentrations of nocodazole alter microtubule dynamic instability in vivo and in vitro.
    Mol Biol Cell. 1997 Jun;8(6):973-85 PMID: 9201709
  14. Drosophila Futsch regulates synaptic microtubule organization and is necessary for synaptic growth.
    Neuron. 2000 May;26(2):371-82 PMID: 10839356
  15. Cytoskeletal reorganization underlying growth cone motility.
    Curr Opin Neurobiol. 1994 Oct;4(5):640-7 PMID: 7849519
  16. Functional cooperation between the microtubule and actin cytoskeletons.
    Curr Opin Cell Biol. 2000 Feb;12(1):63-71 PMID: 10679357
  17. The role of microtubule dynamics in growth cone motility and axonal growth.
    J Cell Biol. 1995 Jan;128(1-2):139-55 PMID: 7822411
  18. Common mechanisms underlying growth cone guidance and axon branching.
    J Neurobiol. 2000 Aug;44(2):145-58 PMID: 10934318
  19. Regulated actin cytoskeleton assembly at filopodium tips controls their extension and retraction.
    J Cell Biol. 1999 Sep 6;146(5):1097-106 PMID: 10477762
  20. Accumulation of actin in subsets of pioneer growth cone filopodia in response to neural and epithelial guidance cues in situ.
    J Cell Biol. 1993 Nov;123(4):935-48 PMID: 8227150
  21. Making the connection: cytoskeletal rearrangements during growth cone guidance.
    Cell. 1995 Oct 20;83(2):171-6 PMID: 7585934
  22. From Abl to actin: Abl tyrosine kinase and associated proteins in growth cone motility.
    Curr Opin Neurobiol. 2000 Feb;10(1):80-7 PMID: 10679439
  23. Growth cone advance is inversely proportional to retrograde F-actin flow.
    Neuron. 1995 Apr;14(4):763-71 PMID: 7536426
  24. Microtubule behavior during guidance of pioneer neuron growth cones in situ.
    J Cell Biol. 1991 Oct;115(2):381-95 PMID: 1918146
  25. Relationship between microtubule dynamics and lamellipodium formation revealed by direct imaging of microtubules in cells treated with nocodazole or taxol.
    Cell Motil Cytoskeleton. 1998;41(4):325-40 PMID: 9858157
  26. Fluorescent speckle microscopy, a method to visualize the dynamics of protein assemblies in living cells.
    Curr Biol. 1998 Nov 5;8(22):1227-30 PMID: 9811609
  27. Composite microtubules of the axon: quantitative analysis of tyrosinated and acetylated tubulin along individual axonal microtubules.
    J Cell Sci. 1993 Feb;104 ( Pt 2):339-52 PMID: 8505364
  28. Endoplasmic reticulum membrane tubules are distributed by microtubules in living cells using three distinct mechanisms.
    Curr Biol. 1998 Jul 2;8(14):798-806 PMID: 9663388
  29. Dynamic instability of microtubule growth.
    Nature. 1984 Nov 15-21;312(5991):237-42 PMID: 6504138
  30. Dynamic behaviors of growth cones extending in the corpus callosum of living cortical brain slices observed with video microscopy.
    J Neurosci. 1994 Apr;14(4):2161-77 PMID: 8158263
  31. Protein kinase C activation promotes microtubule advance in neuronal growth cones by increasing average microtubule growth lifetimes.
    J Cell Biol. 2001 Mar 5;152(5):1033-44 PMID: 11238458
  32. Rac1-dependent actin filament organization in growth cones is necessary for beta1-integrin-mediated advance but not for growth on poly-D-lysine.
    J Neurobiol. 1998 Dec;37(4):524-40 PMID: 9858256
  33. Profilin and the Abl tyrosine kinase are required for motor axon outgrowth in the Drosophila embryo.
    Neuron. 1999 Feb;22(2):291-9 PMID: 10069335
  34. Microtubule release from the centrosome.
    Proc Natl Acad Sci U S A. 1997 May 13;94(10):5078-83 PMID: 9144193
  35. Heterogeneity and stability of local PO2 distribution within the brain tissue.
    Adv Exp Med Biol. 1994;345:567-74 PMID: 8079759
  36. Novel organization of microtubules in cultured central nervous system neurons: formation of hairpin loops at ends of maturing neurites.
    J Neurosci. 1984 Dec;4(12):3002-13 PMID: 6502218
  37. Polymerizing microtubules activate site-directed F-actin assembly in nerve growth cones.
    Mol Biol Cell. 1999 Jul;10(7):2309-27 PMID: 10397767
  38. Microtubule reorganization is obligatory for growth cone turning.
    Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15221-6 PMID: 8986791
  39. Taxol suppresses dynamics of individual microtubules in living human tumor cells.
    Mol Biol Cell. 1999 Apr;10(4):947-59 PMID: 10198049
  40. Birefringence imaging directly reveals architectural dynamics of filamentous actin in living growth cones.
    Mol Biol Cell. 1999 Jan;10(1):197-210 PMID: 9880336
  41. Evidence for microtubule capture by filopodial actin filaments in growth cones.
    Neuroreport. 1991 Oct;2(10):573-6 PMID: 1756237
  42. Microtubule stability decreases axon elongation but not axoplasm production.
    J Neurosci. 1996 May 15;16(10):3236-46 PMID: 8627361
  43. GAP-43 phosphorylation is dynamically regulated in individual growth cones.
    J Neurobiol. 1992 Oct;23(8):1037-53 PMID: 1460463
  44. Actin dynamics and organization during growth cone morphogenesis in Helisoma neurons.
    Cell Motil Cytoskeleton. 1997;37(1):54-71 PMID: 9142439
  45. Structure and organization of membrane organelles along distal microtubule segments in growth cones.
    J Neurosci Res. 1991 Sep;30(1):242-58 PMID: 1795407
  46. Positive feedback interactions between microtubule and actin dynamics during cell motility.
    Curr Opin Cell Biol. 1999 Feb;11(1):61-7 PMID: 10047528
  47. Microtubule "plus-end-tracking proteins": The end is just the beginning.
    Cell. 2001 May 18;105(4):421-4 PMID: 11371339
  48. Microtubule polymerization dynamics.
    Annu Rev Cell Dev Biol. 1997;13:83-117 PMID: 9442869
  49. Fibroblast growth factor-2 promotes axon branching of cortical neurons by influencing morphology and behavior of the primary growth cone.
    J Neurosci. 2001 Jun 1;21(11):3932-41 PMID: 11356881
  50. Substrate-cytoskeletal coupling as a mechanism for the regulation of growth cone motility and guidance.
    J Neurobiol. 2000 Aug;44(2):97-113 PMID: 10934315
  51. Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts.
    Nat Cell Biol. 1999 May;1(1):45-50 PMID: 10559863
  52. A signal transduction pathway involved in microtubule-mediated cell polarization.
    FASEB J. 1999 Dec;13 Suppl 2:S257-60 PMID: 10619139
  53. Assembly of actin-containing cortex occurs at distal regions of growing neurites in PC12 cells.
    J Cell Sci. 1991 Dec;100 ( Pt 4):771-80 PMID: 1814931
  54. 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
  55. Cytoskeleton: CLASPing the end to the edge.
    Curr Biol. 2001 Jun 26;11(12):R477-80 PMID: 11448790
  56. Cdc42-interacting protein 4 mediates binding of the Wiskott-Aldrich syndrome protein to microtubules.
    J Biol Chem. 2000 Mar 17;275(11):7854-61 PMID: 10713100
  57. Interstitial branches develop from active regions of the axon demarcated by the primary growth cone during pausing behaviors.
    J Neurosci. 1998 Oct 1;18(19):7930-40 PMID: 9742160
  58. Different contributions of microtubule dynamics and transport to the growth of axons and collateral sprouts.
    J Neurosci. 1999 May 15;19(10):3860-73 PMID: 10234018
  59. Target selection by cortical axons: alternative mechanisms to establish axonal connections in the developing brain.
    Cold Spring Harb Symp Quant Biol. 1990;55:453-68 PMID: 2132832
  60. Actin filament bundles are required for microtubule reorientation during growth cone turning to avoid an inhibitory guidance cue.
    J Cell Sci. 1996 Aug;109 ( Pt 8):2031-40 PMID: 8856499
  61. Preparation of modified tubulins.
    Methods Enzymol. 1991;196:478-85 PMID: 2034137
  62. Localized sources of neurotrophins initiate axon collateral sprouting.
    J Neurosci. 1998 Jul 15;18(14):5403-14 PMID: 9651222
  63. Reorganization and movement of microtubules in axonal growth cones and developing interstitial branches.
    J Neurosci. 1999 Oct 15;19(20):8894-908 PMID: 10516309
  64. Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone.
    J Cell Biol. 1988 Oct;107(4):1505-16 PMID: 3170637
  65. Direct observation of microtubule-f-actin interaction in cell free lysates.
    J Cell Sci. 1999 Jun;112 ( Pt 12):1947-56 PMID: 10341213
  66. Microtubules remodel actomyosin networks in Xenopus egg extracts via two mechanisms of F-actin transport.
    J Cell Biol. 2000 Jul 24;150(2):361-76 PMID: 10908578
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-12-15
Pages
9757-69
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6763027
Subset
IM
Grants
NIGMS NIH HHS · GM07507 · United States
NINDS NIH HHS · NS14428 · United States
NINDS NIH HHS · NS34270 · United States
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2