Home LiteratureArticle Details
PMID: 24492712 Published · epublish English Journal Article Research Support, N.I.H., Extramural Review

Neuronal signaling through endocytosis.

Cold Spring Harbor perspectives in biology ·Vol. 6 ·No. 2 ·2014-02-01

Cosker KE, Segal RA

Abstract

The distinctive morphology of neurons, with complex dendritic arbors and extensive axons, presents spatial challenges for intracellular signal transduction. The endosomal system provides mechanisms that enable signaling molecules initiated by extracellular cues to be trafficked throughout the expanse of the neuron, allowing intracellular signals to be sustained over long distances. Therefore endosomes are critical for many aspects of neuronal signaling that regulate cell survival, axonal growth and guidance, dendritic branching, and cell migration. An intriguing characteristic of neuronal signal transduction is that endosomal trafficking enables physiological responses that vary based on the subcellular location of signal initiation. In this review, we will discuss the specialized mechanisms and the functional significance of endosomal signaling in neurons, both during normal development and in disease.

MeSH Terms
Cell Survival/physiology Charcot-Marie-Tooth Disease/pathology Endosomes/physiology Humans Huntington Disease/pathology Nerve Growth Factors/physiology Neurons/physiology Receptor, trkA/physiology Signal Transduction/physiology rab GTP-Binding Proteins/physiology
Chemicals
Nerve Growth Factors Receptor, trkA rab GTP-Binding Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Cosker Katharina E
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
Segal Rosalind A
References (70)
70 references, click to expand
  1. Genes for endosomal NHE6 and NHE9 are misregulated in autism brains.
    Mol Psychiatry. 2014 Mar;19(3):277-9 PMID: 23508127
  2. Modulating neuromodulation by receptor membrane traffic in the endocytic pathway.
    Neuron. 2012 Oct 4;76(1):22-32 PMID: 23040804
  3. Mechanisms of endocytosis.
    Annu Rev Biochem. 2009;78:857-902 PMID: 19317650
  4. An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons.
    Science. 1997 Aug 22;277(5329):1097-100 PMID: 9262478
  5. NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway.
    Neuron. 2001 Dec 6;32(5):801-14 PMID: 11738027
  6. The new faces of endocytosis in signaling.
    Traffic. 2012 Jan;13(1):9-18 PMID: 21752167
  7. Pincher-mediated macroendocytosis underlies retrograde signaling by neurotrophin receptors.
    J Neurosci. 2005 May 25;25(21):5236-47 PMID: 15917464
  8. DCTN1 mutations in Perry syndrome.
    Nat Genet. 2009 Feb;41(2):163-5 PMID: 19136952
  9. Long-distance retrograde neurotrophic factor signalling in neurons.
    Nat Rev Neurosci. 2013 Mar;14(3):177-87 PMID: 23422909
  10. Regulation of dynactin through the differential expression of p150Glued isoforms.
    J Biol Chem. 2008 Nov 28;283(48):33611-9 PMID: 18812314
  11. Phosphatidylinositol-3-OH kinases are Rab5 effectors.
    Nat Cell Biol. 1999 Aug;1(4):249-52 PMID: 10559924
  12. Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons.
    Cell. 1994 Mar 25;76(6):1001-11 PMID: 8137419
  13. A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling.
    Cell. 2004 Jul 23;118(2):243-55 PMID: 15260993
  14. BDNF regulates Rab11-mediated recycling endosome dynamics to induce dendritic branching.
    J Neurosci. 2013 Apr 3;33(14):6112-22 PMID: 23554492
  15. Harnessing the power of the endosome to regulate neural development.
    Neuron. 2012 May 10;74(3):440-51 PMID: 22578496
  16. Dynactin is required for transport initiation from the distal axon.
    Neuron. 2012 Apr 26;74(2):331-43 PMID: 22542186
  17. Rapid nuclear responses to target-derived neurotrophins require retrograde transport of ligand-receptor complex.
    J Neurosci. 1999 Sep 15;19(18):7889-900 PMID: 10479691
  18. NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals.
    Neuron. 2003 Jul 3;39(1):69-84 PMID: 12848933
  19. Establishing a novel knock-in mouse line for studying neuronal cytoplasmic dynein under normal and pathologic conditions.
    Cytoskeleton (Hoboken). 2013 Apr;70(4):215-27 PMID: 23475693
  20. Recruitment of actin modifiers to TrkA endosomes governs retrograde NGF signaling and survival.
    Cell. 2011 Aug 5;146(3):421-34 PMID: 21816277
  21. Rab7 mutants associated with Charcot-Marie-Tooth disease exhibit enhanced NGF-stimulated signaling.
    PLoS One. 2010 Dec 09;5(12):e15351 PMID: 21151572
  22. Rab7 mutants associated with Charcot-Marie-Tooth disease cause delayed growth factor receptor transport and altered endosomal and nuclear signaling.
    J Biol Chem. 2013 Jan 11;288(2):1135-49 PMID: 23188822
  23. Endocytic trafficking of neurotrophins in neural development.
    Trends Cell Biol. 2012 May;22(5):266-73 PMID: 22444728
  24. Dynein motors transport activated Trks to promote survival of target-dependent neurons.
    Nat Neurosci. 2004 Jun;7(6):596-604 PMID: 15122257
  25. Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes.
    J Cell Biol. 2002 May 13;157(4):679-91 PMID: 12011113
  26. Self-amplifying autocrine actions of BDNF in axon development.
    Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18430-5 PMID: 22025720
  27. Rab GTPases and microtubule motors.
    Biochem Soc Trans. 2011 Oct;39(5):1202-6 PMID: 21936789
  28. Cbl: many adaptations to regulate protein tyrosine kinases.
    Nat Rev Mol Cell Biol. 2001 Apr;2(4):294-307 PMID: 11283727
  29. PI3KC2α, a class II PI3K, is required for dynamin-independent internalization pathways.
    J Cell Sci. 2010 Dec 15;123(Pt 24):4240-50 PMID: 21081650
  30. Isoform-specific dephosphorylation of dynamin1 by calcineurin couples neurotrophin receptor endocytosis to axonal growth.
    Neuron. 2011 Jun 23;70(6):1085-99 PMID: 21689596
  31. Ca(2+)-dependent activator protein for secretion 2 and autistic-like phenotypes.
    Neurosci Res. 2010 Jul;67(3):197-202 PMID: 20302894
  32. Huntingtin as an essential integrator of intracellular vesicular trafficking.
    Trends Cell Biol. 2009 Apr;19(4):147-55 PMID: 19269181
  33. Microtubule binding by dynactin is required for microtubule organization but not cargo transport.
    J Cell Biol. 2007 Feb 26;176(5):641-51 PMID: 17325206
  34. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules.
    Cell. 2004 Jul 9;118(1):127-38 PMID: 15242649
  35. Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration.
    J Neurosci. 2007 Oct 24;27(43):11758-68 PMID: 17959817
  36. Trk activation of the ERK1/2 kinase pathway stimulates intermediate chain phosphorylation and recruits cytoplasmic dynein to signaling endosomes for retrograde axonal transport.
    J Neurosci. 2012 Oct 31;32(44):15495-510 PMID: 23115187
  37. BAX translocation is a critical event in neuronal apoptosis: regulation by neuroprotectants, BCL-2, and caspases.
    J Neurosci. 1999 Sep 1;19(17):7476-85 PMID: 10460254
  38. Cell survival through Trk neurotrophin receptors is differentially regulated by ubiquitination.
    Neuron. 2006 May 18;50(4):549-59 PMID: 16701206
  39. Trk-signaling endosomes are generated by Rac-dependent macroendocytosis.
    Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12270-5 PMID: 17640889
  40. Membrane trafficking in neuronal maintenance and degeneration.
    Cell Mol Life Sci. 2013 Aug;70(16):2919-34 PMID: 23132096
  41. Endocytosis and molecular sorting.
    Annu Rev Cell Dev Biol. 1996;12:575-625 PMID: 8970738
  42. NT-3, like NGF, is required for survival of sympathetic neurons, but not their precursors.
    Dev Biol. 1999 Jun 15;210(2):411-27 PMID: 10357900
  43. Selectivity in neurotrophin signaling: theme and variations.
    Annu Rev Neurosci. 2003;26:299-330 PMID: 12598680
  44. Action in the axon: generation and transport of signaling endosomes.
    Curr Opin Neurobiol. 2008 Jun;18(3):270-5 PMID: 18778772
  45. High-resolution imaging demonstrates dynein-based vesicular transport of activated Trk receptors.
    J Neurobiol. 2002 Jun 15;51(4):302-12 PMID: 12150505
  46. Moving forward: polarised trafficking in cell migration.
    Trends Cell Biol. 2010 Feb;20(2):71-8 PMID: 20061150
  47. Synaptic vesicle endocytosis.
    Cold Spring Harb Perspect Biol. 2012 Sep 01;4(9):a005645 PMID: 22763746
  48. Numb links extracellular cues to intracellular polarity machinery to promote chemotaxis.
    Dev Cell. 2011 May 17;20(5):610-22 PMID: 21571219
  49. Roles for actin assembly in endocytosis.
    Annu Rev Biochem. 2012;81:661-86 PMID: 22663081
  50. Rab GTPases and their roles in brain neurons and glia.
    Brain Res Rev. 2008 Jun;58(1):236-46 PMID: 18485483
  51. The early steps of endocytosis: from cargo selection to membrane deformation.
    Eur J Cell Biol. 2012 Apr;91(4):226-33 PMID: 21458101
  52. Mutant dynactin in motor neuron disease.
    Nat Genet. 2003 Apr;33(4):455-6 PMID: 12627231
  53. Endocytosis of activated TrkA: evidence that nerve growth factor induces formation of signaling endosomes.
    J Neurosci. 1996 Dec 15;16(24):7950-64 PMID: 8987823
  54. Anterograde transport of brain-derived neurotrophic factor and its role in the brain.
    Nature. 1997 Oct 23;389(6653):856-60 PMID: 9349818
  55. Early endosomal abnormalities and cholinergic neuron degeneration in amyloid-β protein precursor transgenic mice.
    J Alzheimers Dis. 2013;34(3):691-700 PMID: 23254640
  56. Target-derived neurotrophins coordinate transcription and transport of bclw to prevent axonal degeneration.
    J Neurosci. 2013 Mar 20;33(12):5195-207 PMID: 23516285
  57. Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes.
    Mol Biol Cell. 2011 Feb 15;22(4):478-92 PMID: 21169558
  58. The Rab family of proteins: 25 years on.
    Biochem Soc Trans. 2012 Dec 1;40(6):1337-47 PMID: 23176478
  59. Endocytosis.
    Physiol Rev. 1997 Jul;77(3):759-803 PMID: 9234965
  60. A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes.
    J Cell Biol. 2008 Jun 16;181(6):1027-39 PMID: 18559670
  61. Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brain-derived neurotrophic factor.
    J Neurosci. 2004 Apr 28;24(17):4250-8 PMID: 15115821
  62. The molecular motor toolbox for intracellular transport.
    Cell. 2003 Feb 21;112(4):467-80 PMID: 12600311
  63. Dissecting the role of PtdIns(4,5)P2 in endocytosis and recycling of the transferrin receptor.
    J Cell Sci. 2008 May 1;121(Pt 9):1488-94 PMID: 18411250
  64. Mutant Huntingtin alters retrograde transport of TrkB receptors in striatal dendrites.
    J Neurosci. 2013 Apr 10;33(15):6298-309 PMID: 23575829
  65. Endocytosis regulates cell soma translocation and the distribution of adhesion proteins in migrating neurons.
    PLoS One. 2011 Mar 22;6(3):e17802 PMID: 21445347
  66. A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w.
    J Neurosci. 2009 May 20;29(20):6700-9 PMID: 19458239
  67. Retrograde axonal transport: pathways to cell death?
    Trends Neurosci. 2010 Jul;33(7):335-44 PMID: 20434225
  68. Spatially and functionally distinct roles of the PI3-K effector pathway during NGF signaling in sympathetic neurons.
    Neuron. 2000 Sep;27(3):499-512 PMID: 11055433
  69. Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors.
    Neuron. 2007 Jul 5;55(1):53-68 PMID: 17610817
  70. A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA.
    Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9909-14 PMID: 9275225
Article Info
Journal
Cold Spring Harbor perspectives in biology
Abbr.
Cold Spring Harb Perspect Biol
ISSN
1943-0264
DOI
10.1101/cshperspect.a020669
Published
2014-02-01
Epub
2014-00-01
Language
English
Region
United States
NLM ID
101513680
PMCID
PMC3941234
Subset
IM
Grants
NINDS NIH HHS · R01 NS050674 · United States
External Links
PubMed source DOI: 10.1101/cshperspect.a020669 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: [email protected]

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