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Abstract #14670 Published in IGR 8-4
Optineurin increases cell survival and translocates to the nucleus in a Rab8-dependent manner upon an apoptotic stimulus
De Marco N; Buono M; Troise F; Diez Roux GJournal of Biological Chemistry 2006; 281: 16147-16156
In glaucoma the retinal ganglion cells of the retina die through the induction of apoptosis leading to excavation of the optic nerve and blindness. Mutations in the optineurin (optic neuropathy inducing) protein were found associated with an adult form of glaucoma. To date, the role of optineurin in the neurodegeneration process that occurs during glaucoma is still unknown. We now report that in response to an apoptotic stimulus, optineurin changes subcellular localization and translocates from the Golgi to the nucleus. This translocation is dependent on the GTPase activity of Rab8, an interactor of optineurin. Furthermore, we demonstrate that the overexpression of optineurin protects cells from H2 O2 -induced cell death and blocks cytochrome c release from the mitochondria. A mutated form of optineurin, E50K, identified in normal tension glaucoma patients loses its ability to translocate to the nucleus and when overexpressed compromises the mitochondrial membrane integrity resulting in cells that are less fit to survive under stress conditions. The correlation between optineurin function and cell survival will be key to begin to understand retinal ganglion cell biology and signaling and to design general 'survival' strategies to treat a disease of such a complex etiology as glaucoma.
Dr. G. Diez-Roux, Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Napoli, Italy
Classification:
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
3.6 Cellular biology (Part of: 3 Laboratory methods)
