Metallothionein-IIA promotes neurite growth via the megalin receptor.
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 microm (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.
Fitzgerald
Melinda
M
Experimental and Regenerative Neurosciences, School of Animal Biology, University of Western Australia, Hackett Drive, Crawley 6009, WA, Australia. melfitz1@cyllene.uwa.edu.au
Nairn
Pia
P
Bartlett
Carole A
CA
Chung
Roger S
RS
West
Adrian K
AK
Beazley
Lyn D
LD
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000276:immunology / Q000502:physiology*; D008297:Male; D008668:Metallothionein / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D008668:Metallothionein