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Long-distance retrograde neurotrophic factor signalling in neurons - Nature Reviews Neuroscience

  • ️Ginty, David D.
  • ️Wed Feb 20 2013
  • Huang, E. J. & Reichardt, L. F. Neurotrophins: roles in neuronal development and function. Annu. Rev. Neurosci. 24, 677–736 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Michaelevski, I., Medzihradszky, K. F., Lynn, A., Burlingame, A. L. & Fainzilber, M. Axonal transport proteomics reveals mobilization of translation machinery to the lesion site in injured sciatic nerve. Mol. Cell Proteomics 9, 976–987 (2010).

    Article  CAS  PubMed  Google Scholar 

  • De Vos, K. J., Grierson, A. J., Ackerley, S. & Miller, C. C. Role of axonal transport in neurodegenerative diseases. Annu. Rev. Neurosci. 31, 151–173 (2008). This articles provides an excellent review of the pathological effects caused by defects in the axonal transport process as they pertain to various neurodegenerative diseases.

    Article  CAS  PubMed  Google Scholar 

  • Hamburger, V. & Levi-Montalcini, R. Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J. Exp. Zool. 111, 457–501 (1949).

    Article  CAS  PubMed  Google Scholar 

  • Oppenheim, R. W. The neurotrophic theory and naturally occurring motoneuron death. Trends Neurosci. 12, 252–255 (1989).

    Article  CAS  PubMed  Google Scholar 

  • Buss, R. R. & Oppenheim, R. W. Role of programmed cell death in normal neuronal development and function. Anat. Sci. Int. 79, 191–197 (2004).

    Article  PubMed  Google Scholar 

  • Barde, Y. A. Trophic factors and neuronal survival. Neuron 2, 1525–1534 (1989).

    Article  CAS  PubMed  Google Scholar 

  • Snider, W. D. Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77, 627–638 (1994).

    Article  PubMed  Google Scholar 

  • Wright, D. E., Zhou, L., Kucera, J. & Snider, W. D. Introduction of a neurotrophin-3 transgene into muscle selectively rescues proprioceptive neurons in mice lacking endogenous neurotrophin-3. Neuron 19, 503–517 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Davis, B. M., Goodness, T. P., Soria, A. & Albers, K. M. Over-expression of NGF in skin causes formation of novel sympathetic projections to trkA-positive sensory neurons. Neuroreport 9, 1103–1107 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Heumann, R., Korsching, S., Scott, J. & Thoenen, H. Relationship between levels of nerve growth factor (NGF) and its messenger RNA in sympathetic ganglia and peripheral target tissues. EMBO J. 3, 3183–3189 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shelton, D. L. & Reichardt, L. F. Expression of the β-nerve growth factor gene correlates with the density of sympathetic innervation in effector organs. Proc. Natl Acad. Sci. USA 81, 7951–7955 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farinas, I., Yoshida, C. K., Backus, C. & Reichardt, L. F. Lack of neurotrophin-3 results in death of spinal sensory neurons and premature differentiation of their precursors. Neuron 17, 1065–1078 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hendry, I. A. & Campbell, J. Morphometric analysis of rat superior cervical ganglion after axotomy and nerve growth factor treatment. J. Neurocytol. 5, 351–360 (1976).

    Article  CAS  PubMed  Google Scholar 

  • Vestergaard, S., Tandrup, T. & Jakobsen, J. Effect of permanent axotomy on number and volume of dorsal root ganglion cell bodies. J. Comp. Neurol. 388, 307–312 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Stockel, K., Paravicini, U. & Thoenen, H. Specificity of the retrograde axonal transport of nerve growth factor. Brain Res. 76, 413–421 (1974).

    Article  CAS  PubMed  Google Scholar 

  • DiStefano, P. S. et al. The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons. Neuron 8, 983–993 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Sandow, S. L. et al. Signalling organelle for retrograde axonal transport of internalized neurotrophins from the nerve terminal. Immunol. Cell Biol. 78, 430–435 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Hendry, I. A., Stockel, K., Thoenen, H. & Iversen, L. L. The retrograde axonal transport of nerve growth factor. Brain Res. 68, 103–121 (1974).

    Article  CAS  PubMed  Google Scholar 

  • Campenot, R. B. Local control of neurite development by nerve growth factor. Proc. Natl Acad. Sci. USA 74, 4516–4519 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye, H., Kuruvilla, R., Zweifel, L. S. & Ginty, D. D. Evidence in support of signaling endosome-based retrograde survival of sympathetic neurons. Neuron 39, 57–68 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Mok, S. A. & Campenot, R. B. A nerve growth factor-induced retrograde survival signal mediated by mechanisms downstream of TrkA. Neuropharmacology 52, 270–278 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Zweifel, L. S., Kuruvilla, R. & Ginty, D. D. Functions and mechanisms of retrograde neurotrophin signalling. Nature Rev. Neurosci. 6, 615–625 (2005).

    Article  CAS  Google Scholar 

  • Park, J. W., Vahidi, B., Taylor, A. M., Rhee, S. W. & Jeon, N. L. Microfluidic culture platform for neuroscience research. Nature Protoc. 1, 2128–2136 (2006).

    Article  CAS  Google Scholar 

  • Atwal, J. K., Massie, B., Miller, F. D. & Kaplan, D. R. The TrkB-Shc site signals neuronal survival and local axon growth via MEK and PI3-kinase. Neuron 27, 265–277 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Kuruvilla, R., Ye, H. & Ginty, D. D. Spatially and functionally distinct roles of the PI3-K effector pathway during NGF signaling in sympathetic neurons. Neuron 27, 499–512 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Riccio, A., Pierchala, B. A., Ciarallo, C. L. & Ginty, D. D. An NGF–TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons. Science 277, 1097–1100 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Pazyra-Murphy, M. F. et al. A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w. J. Neurosci. 29, 6700–6709 (2009). The authors describe a retrograde-specific transcriptional response initiated by neurotrophins that is important for neuronal survival.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Putcha, G. V., Deshmukh, M. & Johnson, E. M. Jr. BAX translocation is a critical event in neuronal apoptosis: regulation by neuroprotectants, BCL-2, and caspases. J. Neurosci. 19, 7476–7485 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nikoletopoulou, V. et al. Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not. Nature 467, 59–63 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Deppmann, C. D. et al. A model for neuronal competition during development. Science 320, 369–373 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mandai, K. et al. LIG family receptor tyrosine kinase-associated proteins modulate growth factor signals during neural development. Neuron 63, 614–627 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh, K. K. et al. Developmental axon pruning mediated by BDNF–p75NTR-dependent axon degeneration. Nature Neurosci. 11, 649–658 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Sharma, N. et al. Long-distance control of synapse assembly by target-derived NGF. Neuron 67, 422–434 (2010). In this article, the authors propose a novel function for retrograde neurotrophin signalling in controlling upstream synapse formation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ladle, D. R., Pecho-Vrieseling, E. & Arber, S. Assembly of motor circuits in the spinal cord: driven to function by genetic and experience-dependent mechanisms. Neuron 56, 270–283 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Patel, T. D. et al. Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive sensory afferents. Neuron 38, 403–416 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Luo, W. et al. A hierarchical NGF signaling cascade controls Ret-dependent and Ret-independent events during development of nonpeptidergic DRG neurons. Neuron 54, 739–754 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Bodmer, D., Ascano, M. & Kuruvilla, R. Isoform-specific dephosphorylation of dynamin1 by calcineurin couples neurotrophin receptor endocytosis to axonal growth. Neuron 70, 1085–1099 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lonze, B. E., Riccio, A., Cohen, S. & Ginty, D. D. Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB. Neuron 34, 371–385 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Wickramasinghe, S. R. et al. Serum response factor mediates NGF-dependent target innervation by embryonic DRG sensory neurons. Neuron 58, 532–545 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Graef, I. A. et al. Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons. Cell 113, 657–670 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Patel, T. D., Jackman, A., Rice, F. L., Kucera, J. & Snider, W. D. Development of sensory neurons in the absence of NGF/TrkA signaling in vivo. Neuron 25, 345–357 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Glebova, N. O. & Ginty, D. D. Heterogeneous requirement of NGF for sympathetic target innervation in vivo. J. Neurosci. 24, 743–751 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuruvilla, R. et al. A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Cell 118, 243–255 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Courchesne, S. L., Karch, C., Pazyra-Murphy, M. F. & Segal, R. A. Sensory neuropathy attributable to loss of Bcl-w. J. Neurosci. 31, 1624–1634 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Voyvodic, J. T. Peripheral target regulation of dendritic geometry in the rat superior cervical ganglion. J. Neurosci. 9, 1997–2010 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Purves, D. Functional and structural changes in mammalian sympathetic neurones following interruption of their axons. J. Physiol. 252, 429–463 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vrieseling, E. & Arber, S. Target-induced transcriptional control of dendritic patterning and connectivity in motor neurons by the ETS gene Pea3. Cell 127, 1439–1452 (2006). Here, the authors demonstrate that retrograde growth factor (specifically, GDNF) signalling activates a transcriptional programme leading to specific patterns of motor neuron dendrite arborization.

    Article  CAS  PubMed  Google Scholar 

  • Lom, B., Cogen, J., Sanchez, A. L., Vu, T. & Cohen-Cory, S. Local and target-derived brain-derived neurotrophic factor exert opposing effects on the dendritic arborization of retinal ganglion cells in vivo. J. Neurosci. 22, 7639–7649 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo, T. et al. An evolving NGF–Hoxd1 signaling pathway mediates development of divergent neural circuits in vertebrates. Nature Neurosci. 14, 31–36 (2011).

    Article  CAS  PubMed  Google Scholar 

  • Luo, W., Enomoto, H., Rice, F. L., Milbrandt, J. & Ginty, D. D. Molecular identification of rapidly adapting mechanoreceptors and their developmental dependence on ret signaling. Neuron 64, 841–856 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin, J. H. et al. Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression. Cell 95, 393–407 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Apostolova, G. & Dechant, G. Development of neurotransmitter phenotypes in sympathetic neurons. Auton. Neurosci. 151, 30–38 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Curtis, R. et al. Neuronal injury increases retrograde axonal transport of the neurotrophins to spinal sensory neurons and motor neurons via multiple receptor mechanisms. Mol. Cell Neurosci. 12, 105–118 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Ehlers, M. D., Kaplan, D. R., Price, D. L. & Koliatsos, V. E. NGF-stimulated retrograde transport of trkA in the mammalian nervous system. J. Cell Biol. 130, 149–156 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Watson, F. L. et al. Rapid nuclear responses to target-derived neurotrophins require retrograde transport of ligand-receptor complex. J. Neurosci. 19, 889–7900 (1999).

    Article  Google Scholar 

  • Yuen, E. C., Howe, C. L., Li, Y., Holtzman, D. M. & Mobley, W. C. Nerve growth factor and the neurotrophic factor hypothesis. Brain Dev. 18, 362–368 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Howe, C. L. & Mobley, W. C. Signaling endosome hypothesis: a cellular mechanism for long distance communication. J. Neurobiol. 58, 207–216 (2004).

    Article  PubMed  Google Scholar 

  • Halegoua, S., Armstrong, R. C. & Kremer, N. E. Dissecting the mode of action of a neuronal growth factor. Curr. Top. Microbiol. Immunol. 165, 119–170 (1991).

    CAS  PubMed  Google Scholar 

  • MacInnis, B. L. & Campenot, R. B. Retrograde support of neuronal survival without retrograde transport of nerve growth factor. Science 295, 1536–1539 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Grimes, M. L. et al. Endocytosis of activated TrkA: evidence that nerve growth factor induces formation of signaling endosomes. J. Neurosci. 16, 7950–7964 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doherty, G. J. & McMahon, H. T. Mechanisms of endocytosis. Annu. Rev. Biochem. 78, 857–902 (2009).

    CAS  PubMed  Google Scholar 

  • Howe, C. L., Valletta, J. S., Rusnak, A. S. & Mobley, W. C. NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras–MAPK pathway. Neuron 32, 801–814 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Shao, Y. et al. Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes. J. Cell Biol. 157, 679–691 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orth, J. D., Krueger, E. W., Weller, S. G. & McNiven, M. A. A novel endocytic mechanism of epidermal growth factor receptor sequestration and internalization. Cancer Res. 66, 3603–3610 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Valdez, G. et al. Pincher-mediated macroendocytosis underlies retrograde signaling by neurotrophin receptors. J. Neurosci. 25, 5236–5247 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaplan, D. R. & Miller, F. D. Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 10, 381–391 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Krag, C., Malmberg, E. K. & Salcini, A. E. PI3KC2α, a class II PI3K, is required for dynamin-independent internalization pathways. J. Cell Sci. 123, 4240–4250 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Christoforidis, S. et al. Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nature Cell Biol. 1, 249–252 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Abe, N., Inoue, T., Galvez, T., Klein, L. & Meyer, T. Dissecting the role of PtdIns(4,5)P2 in endocytosis and recycling of the transferrin receptor. J. Cell Sci. 121, 1488–1494 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Radhakrishnan, A., Stein, A., Jahn, R. & Fasshauer, D. The Ca2+ affinity of synaptotagmin 1 is markedly increased by a specific interaction of its C2B domain with phosphatidylinositol 4,5-bisphosphate. J. Biol. Chem. 284, 25749–25760 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y., Moheban, D. B., Conway, B. R., Bhattacharyya, A. & Segal, R. A. Cell surface Trk receptors mediate NGF-induced survival while internalized receptors regulate NGF-induced differentiation. J. Neurosci. 20, 5671–5678 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bethoney, K. A., King, M. C., Hinshaw, J. E., Ostap, E. M. & Lemmon, M. A. A possible effector role for the pleckstrin homology (PH) domain of dynamin. Proc. Natl Acad. Sci. USA 106, 13359–13364 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vetter, M. L., Martin-Zanca, D., Parada, L. F., Bishop, J. M. & Kaplan, D. R. Nerve growth factor rapidly stimulates tyrosine phosphorylation of phospholipase C-γ1 by a kinase activity associated with the product of the trk protooncogene. Proc. Natl Acad. Sci. USA 88, 5650–5654 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bunney, T. D. & Katan, M. PLC regulation: emerging pictures for molecular mechanisms. Trends Biochem. Sci. 36, 88–96 (2011).

    Article  CAS  PubMed  Google Scholar 

  • Choi, J. H. et al. Phospholipase C-γ1 is a guanine nucleotide exchange factor for dynamin-1 and enhances dynamin-1-dependent epidermal growth factor receptor endocytosis. J. Cell Sci. 117, 3785–3795 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Zerial, M. & McBride, H. Rab proteins as membrane organizers. Nature Rev. Mol. Cell Biol. 2, 107–117 (2001).

    Article  CAS  Google Scholar 

  • Gorvel, J. P., Chavrier, P., Zerial, M. & Gruenberg, J. rab5 controls early endosome fusion in vitro. Cell 64, 915–925 (1991).

    Article  CAS  PubMed  Google Scholar 

  • Bucci, C. et al. The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell 70, 715–728 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Bucci, C., Thomsen, P., Nicoziani, P., McCarthy, J. & van Deurs, B. Rab7: a key to lysosome biogenesis. Mol. Biol. Cell 11, 467–480 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rink, J., Ghigo, E., Kalaidzidis, Y. & Zerial, M. Rab conversion as a mechanism of progression from early to late endosomes. Cell 122, 735–749 (2005). An important study demonstrating a switch in RAB proteins during maturation of endosomes.

    Article  CAS  PubMed  Google Scholar 

  • Claude, P., Hawrot, E., Dunis, D. A. & Campenot, R. B. Binding, internalization, and retrograde transport of 125I-nerve growth factor in cultured rat sympathetic neurons. J. Neurosci. 2, 431–442 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deinhardt, K. et al. Rab5 and Rab7 control endocytic sorting along the axonal retrograde transport pathway. Neuron 52, 293–305 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Chen, X. Q. et al. Endosome-mediated retrograde axonal transport of P2X3 receptor signals in primary sensory neurons. Cell Res. 22, 677–696 (2011).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Harrington, A. W. et al. Recruitment of actin modifiers to TrkA endosomes governs retrograde NGF signaling and survival. Cell 146, 421–434 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu, C., Lai, C. F. & Mobley, W. C. Nerve growth factor activates persistent Rap1 signaling in endosomes. J. Neurosci. 21, 5406–5416 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delcroix, J. D. et al. NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals. Neuron 39, 69–84 (2003). In this article, the authors characterize the retrogradely transported NGF vesicle in sciatic nerve, showing that it associates with components of TRKA signalling pathways and has properties of an early endosome.

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharyya, A. et al. High-resolution imaging demonstrates dynein-based vesicular transport of activated Trk receptors. J. Neurobiol. 51, 302–312 (2002).

    Article  CAS  PubMed  Google Scholar 

  • O'Brien, J. J. & Nathanson, N. M. Retrograde activation of STAT3 by leukemia inhibitory factor in sympathetic neurons. J. Neurochem. 103, 288–302 (2007).

    CAS  PubMed  Google Scholar 

  • Murphy, P. G., Grondin, J., Altares, M. & Richardson, P. M. Induction of interleukin-6 in axotomized sensory neurons. J. Neurosci. 15, 5130–5138 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walker, B. A., Ji, S. J. & Jaffrey, S. R. Intra-axonal translation of RhoA promotes axon growth inhibition by CSPG. J. Neurosci. 32, 14442–14447 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith, R. B., Machamer, J. B., Kim, N. C., Hays, T. S. & Marques, G. Relay of retrograde synaptogenic signals through axonal transport of BMP receptors. J. Cell Sci. 125, 3752–3764 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox, L. J., Hengst, U., Gurskaya, N. G., Lukyanov, K. A. & Jaffrey, S. R. Intra-axonal translation and retrograde trafficking of CREB promotes neuronal survival. Nature Cell Biol. 10, 149–159 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Andreassi, C. et al. An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons. Nature Neurosci. 13, 291–301 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Deinhardt, K., Reversi, A., Berninghausen, O., Hopkins, C. R. & Schiavo, G. Neurotrophins redirect p75NTR from a clathrin-independent to a clathrin-dependent endocytic pathway coupled to axonal transport. Traffic 8, 1736–1749 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Salehi, A. et al. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51, 29–42 (2006). An important article providing evidence for the idea that defects in NGF axonal transport are a contributing factor in the pathogenesis of Alzhiemer's disease.

    Article  CAS  PubMed  Google Scholar 

  • Cooper, J. D. et al. Failed retrograde transport of NGF in a mouse model of Down's syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proc. Natl Acad. Sci. USA 98, 10439–10444 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Counts, S. E. et al. Reduction of cortical TrkA but not p75NTR protein in early-stage Alzheimer's disease. Ann. Neurol. 56, 520–531 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Svendsen, C. N., Cooper, J. D. & Sofroniew, M. V. Trophic factor effects on septal cholinergic neurons. Ann. NY Acad. Sci. 640, 91–94 (1991).

    Article  CAS  PubMed  Google Scholar 

  • Topp, J. D., Gray, N. W., Gerard, R. D. & Horazdovsky, B. F. Alsin is a Rab5 and Rac1 guanine nucleotide exchange factor. J. Biol. Chem. 279, 24612–24623 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Devon, R. S. et al. Als2-deficient mice exhibit disturbances in endosome trafficking associated with motor behavioral abnormalities. Proc. Natl Acad. Sci. USA 103, 9595–9600 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cogli, L., Piro, F. & Bucci, C. Rab7 and the CMT2B disease. Biochem. Soc. Trans. 37, 1027–1031 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Cogli, L. et al. CMT2B-associated Rab7 mutants inhibit neurite outgrowth. Acta Neuropathol. 120, 491–501 (2010).

    Article  CAS  PubMed  Google Scholar 

  • BasuRay, S., Mukherjee, S., Romero, E., Wilson, M. C. & Wandinger-Ness, A. Rab7 mutants associated with Charcot-Marie-Tooth disease exhibit enhanced NGF-stimulated signaling. PLoS ONE 5, e15351 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar