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Metallothionein-IIA promotes neurite growth via the megalin receptor


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

DOI: doi:10.1007/s00221-007-1032-y


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. © 2007 Springer-Verlag.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Chung, RS (Associate Professor Roger Chung)
UTAS Author:West, AK (Professor Adrian West)
ID Code:45097
Year Published:2007
Web of Science® Times Cited:56
Deposited By:Menzies Institute for Medical Research
Deposited On:2007-08-01
Last Modified:2009-08-25

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