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Metallothionein-IIA promotes neurite growth via the megalin receptor


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Fitzgerald, M and Nairn, P and Bartlett, C and Chung, RS and West, AK and Beazley, LD (2007) Metallothionein-IIA promotes neurite growth via the megalin receptor. Experimental Brain Research, 183 (2). pp. 171-180. ISSN 0014-4819

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Metallothionein (MT)-I/II has been shown to be neuroprotective and neuroregenerative in a model of rat cortical brain injury. Here we examine expression patterns of MT-I/II and its putative receptor megalin in rat retina. At neonatal stages, MT-I/II was present in retinal ganglion cells (RGCs) but not glial or amacrine cells; megalin was present throughout the retina. Whilst MT-I/II was absent from adult RGC in normal animals and after optic nerve transection, the constitutive megalin expression in RGCs was lost following optic nerve transection. In vitro MT-IIA treatment stimulated neuritic growth: more RGCs grew neurites longer than 25 μm (P < 0.05) in dissociated retinal cultures and neurite extension increased in retinal explants (P < 0.05). MT-IIA treatment of mixed retinal cultures increased megalin expression in RGCs, and pre-treating cells with anti-megalin antibodies prevented MT-IIA-stimulated neurite extension. Our results indicate that MT-IIA stimulates neurite outgrowth in RGCs and may do so via the megalin receptor; we propose that neurite extension is triggered via signal transduction pathways activated by the NPxY motifs of megalin’s cytoplasmic tail.

Item Type: Article
Journal or Publication Title: Experimental Brain Research
Page Range: pp. 171-180
ISSN: 0014-4819
Identification Number - DOI: 10.1007/s00221-007-1032-y
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Date Deposited: 22 Jul 2008 04:45
Last Modified: 18 Nov 2014 03:45
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