Overexpression of GAP-43 modifies the distribution of the receptors for myelin-associated growth-inhibitory proteins in injured Purkinje axons - PubMed (original) (raw)
Overexpression of GAP-43 modifies the distribution of the receptors for myelin-associated growth-inhibitory proteins in injured Purkinje axons
Simona Foscarin et al. Eur J Neurosci. 2009 Nov.
Abstract
Abstract Neurons with enhanced intrinsic growth capabilities can elongate their axons into non-permissive territories, but the mechanisms that enable the outgrowing processes to overcome environmental inhibition are largely unknown. To address this issue, we examined adult mouse Purkinje cells that overexpress the axonal growth-associated protein GAP-43. After injury, these neurons exhibit sprouting along the intracortical neuritic course and at the severed stump in the white matter. To determine whether GAP-43-overexpressing Purkinje cells are responsive to extrinsic inhibitory cues, we investigated the content and subcellular localization of major receptors for myelin-associated inhibitory proteins, PlexinB1 and the Nogo receptor (NgR) with the related co-receptors LINGO-1 and p75. Expression of these molecules, estimated by measuring perikaryal immunostaining intensity and Western blot, was not different in wild-type or transgenic mice, and it was not overtly modified after axotomy. Following injury, however, the content of PlexinB1 was significantly reduced in GAP-43-overexpressing neurites. Furthermore, in the same axons the distribution of both PlexinB1 and NgR was altered, being inverse to that of GAP-43. Labelling for the two receptors was conspicuously reduced on the axonal surface and it was almost undetectable in the outgrowing sprouts, which showed strong GAP-43 immunoreactivity. These observations indicate that although GAP-43 overexpression does not modify the expression of receptors for myelin-associated inhibitory factors, it interferes with their subcellular localization and exposure on the neuritic membrane. Therefore, GAP-43 promotes axon growth by multiple synergistic mechanisms that potentiate the intrinsic motility of the elongating processes, while reducing their sensitivity to environmental inhibition.
Similar articles
- GAP-43 overexpression in adult mouse Purkinje cells overrides myelin-derived inhibition of neurite growth.
Gianola S, Rossi F. Gianola S, et al. Eur J Neurosci. 2004 Feb;19(4):819-30. doi: 10.1111/j.0953-816x.2004.03190.x. Eur J Neurosci. 2004. PMID: 15009129 - Neurite-myelin interaction in the control of purkinje axon growth and regeneration.
Gianola S, Rossi F. Gianola S, et al. Ann N Y Acad Sci. 2005 Jun;1048:141-8. doi: 10.1196/annals.1342.013. Ann N Y Acad Sci. 2005. PMID: 16154928 - Targeted overexpression of the neurite growth-associated protein B-50/GAP-43 in cerebellar Purkinje cells induces sprouting after axotomy but not axon regeneration into growth-permissive transplants.
Buffo A, Holtmaat AJ, Savio T, Verbeek JS, Oberdick J, Oestreicher AB, Gispen WH, Verhaagen J, Rossi F, Strata P. Buffo A, et al. J Neurosci. 1997 Nov 15;17(22):8778-91. doi: 10.1523/JNEUROSCI.17-22-08778.1997. J Neurosci. 1997. PMID: 9348347 Free PMC article. - Mechanisms of axonal plasticity.
Strata P, Buffo A, Rossi F. Strata P, et al. Arch Ital Biol. 1999 May;137(2-3):181-92. Arch Ital Biol. 1999. PMID: 10349496 Review. - The Nogo-66 receptor: focusing myelin inhibition of axon regeneration.
McGee AW, Strittmatter SM. McGee AW, et al. Trends Neurosci. 2003 Apr;26(4):193-8. doi: 10.1016/S0166-2236(03)00062-6. Trends Neurosci. 2003. PMID: 12689770 Review.
Cited by
- Semaphorins in Adult Nervous System Plasticity and Disease.
Carulli D, de Winter F, Verhaagen J. Carulli D, et al. Front Synaptic Neurosci. 2021 May 11;13:672891. doi: 10.3389/fnsyn.2021.672891. eCollection 2021. Front Synaptic Neurosci. 2021. PMID: 34045951 Free PMC article. Review. - The Chemorepulsive Protein Semaphorin 3A and Perineuronal Net-Mediated Plasticity.
de Winter F, Kwok JC, Fawcett JW, Vo TT, Carulli D, Verhaagen J. de Winter F, et al. Neural Plast. 2016;2016:3679545. doi: 10.1155/2016/3679545. Epub 2016 Jan 14. Neural Plast. 2016. PMID: 27057361 Free PMC article. Review. - Purkinje cell axonal anatomy: quantifying morphometric changes in essential tremor versus control brains.
Babij R, Lee M, Cortés E, Vonsattel JP, Faust PL, Louis ED. Babij R, et al. Brain. 2013 Oct;136(Pt 10):3051-61. doi: 10.1093/brain/awt238. Epub 2013 Sep 12. Brain. 2013. PMID: 24030953 Free PMC article. - Lingo-1 expression is increased in essential tremor cerebellum and is present in the basket cell pinceau.
Kuo SH, Tang G, Louis ED, Ma K, Babji R, Balatbat M, Cortes E, Vonsattel JP, Yamamoto A, Sulzer D, Faust PL. Kuo SH, et al. Acta Neuropathol. 2013 Jun;125(6):879-89. doi: 10.1007/s00401-013-1108-7. Epub 2013 Mar 31. Acta Neuropathol. 2013. PMID: 23543187 Free PMC article. - Capsaicin-induced activation of ERK1/2 and its involvement in GAP-43 expression and CGRP depletion in organotypically cultured DRG neurons.
Li Y, Liu G, Li H, Xu Y, Zhang H, Liu Z. Li Y, et al. Cell Mol Neurobiol. 2013 Apr;33(3):433-41. doi: 10.1007/s10571-013-9909-8. Epub 2013 Feb 21. Cell Mol Neurobiol. 2013. PMID: 23430271
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous