@article{epprod7070, volume = {183}, number = {2}, month = {["lib/utils:month\verb1_17070" not defined]}, author = {M Fitzgerald and P Nairn and C Bartlett and RS Chung and AK West and LD Beazley}, note = {The original publication is available at www.springerlink.com}, title = {Metallothionein-IIA promotes neurite growth via the megalin receptor}, year = {2007}, journal = {Experimental Brain Research}, pages = {171--180}, url = {http://eprints.utas.edu.au/7070/}, abstract = {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 ?m (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.} }