1 / 20

NF2 and Merlin

NF2 and Merlin. Victoria Beasley March 20, 2007. Neurofibromatosis 2 (NF2) – dominantly inherited disease characterized by nervous tissue tumors Merlin –moesin, ezrin, radixin-like protein ERMs – ezrin, radixin, and moesin Membrane-cytoskeleton-associated proteins. Glossary.

libba
Download Presentation

NF2 and Merlin

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. NF2 and Merlin Victoria Beasley March 20, 2007

  2. Neurofibromatosis 2 (NF2) – dominantly inherited disease characterized by nervous tissue tumors Merlin –moesin, ezrin, radixin-like protein ERMs – ezrin, radixin, and moesin Membrane-cytoskeleton-associated proteins Glossary

  3. Elements of the disease, Neurofibromatosis 2 NF2/Merlin’s gene family and its normal function Merlin’s role in cancer Summary of important points What we’ll go over today

  4. Neurofibromatosis 2 Acoustic neuroma Schwannoma http://www.tinnitusformula.com/qtimes/neuroma.jpg

  5. 1 in 33,000 to 40,000 people affected Typically presents as a hearing problem Current treatment options Surgery Radiation and chemotherapy Genetic screening Facts and figures

  6. Cytoskeletal association Cell-cell communication Located at adherens junctions Monitors cell-cell contact → growth inhibition Cell-ECM communication Embryonic development Normal function of Merlin in Humans

  7. Growth Inhibition Growth

  8. Growth Inhibition Growth

  9. Homology: FERM Domain

  10. Loss of contact inhibition → Proliferation Irregular cell-ECM interaction → Possible link to metastasis Merlin deficiency and human cancer

  11. Nf2+/- mice: no schwannomas osteosarcomas not a phenotypically accurate model for the human NF2 disease Murine NF2 and Merlin

  12. Nf2 -/- mice: lethal at day 6.5 Collapsed extraembryonic region just before gastrulation Absence of organized ectoderm Murine NF2 and Merlin

  13. Murine NF2 and Merlin:Lethal at Day 6.5 http://www.nature.com/ng/journal/v27/n4/images/ng0401_351_I1.gif

  14. What happens locally to the actin cytoskeleton at the site of concentrated active or defective Merlin? How do ERMs and Merlin interact? Are there other Merlin-like proteins instrumental in other cancers? Key questions remain…

  15. NF2 is a tumor suppressor gene Mutations in NF2 eliminate Merlin expression Merlin deficiency affects cell motility and proliferation Merlin plays a key role in embryonic development Take-home points

  16. Xiao GH, Chernoff J, and Testa JR, 2003. NF2: The Wizardry of Merlin. Genes, Chromosomes, & Cancer 38:389-399. Sun CX, Robb VA, Gutmann DH, 2002. Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation. Journal of Cell Science 115, 3991-4000. The Company of Biologists Ltd doi:10.1242/jcs.0094. McClatchey, Andrea I, 2003.. Merlin and ERM proteins: unappreciated roles in cancer development? Nature Reviews: Cancer. Vol. 3: 877-884. http://focus.hms.harvard.edu/2001/Jul13_2001/research_briefs.html Crystal structure of FERM. http://www.cytoskeletons.com/structure.php?start=200. http://www.cellsignal.com/products/9168.html http://www.masstechportal.org/IP575.aspx http://www.pnas.org/cgi/content/full/101/52/18200 http://mcb.asm.org/cgi/content/full/25/6/2384?ck=nck Bibliography

  17. Questions?

More Related