ErbB2 Trafficking and Signaling in Human Vestibular Schwannomas
Abstract
During the first year of the award we have made substantial progress in achieving the aims of the proposal. I will discuss the progress for each aim of the proposal. Determine the ability of merlin to regulate ErbB2 localization and activity in vestibular schwannoma (VS) cells. Until recently we were unable to use human vestibular schwannoma (VS) specimens while we were working to obtain Human Subjects approval. During this period, we focused on correlating the status of merlin phosphorylation with ErbB2 trafficking in normal Schwann cells (SCs). First, we determined that the trafficking of ErbB2 into lipid rafts in SCs correlates with loss of axonal contact, phosphorylation of merlin on Serine 518, and proliferation (Figs 1 and 2). Thus, phosphorylation of merlin on Serine 518 (S518), which inhibits its growth suppressive function, is correlated with the movement of ErbB2 into lipid rafts in the cell membrane. We have previously shown that ErbB2 constitutively resides in lipid rafts in human vestibular schwannoma cells that lack functional merlin (Brown and Hansen, Otology & Neurotology, in press). Since we did not initially have approval to work with human VS specimens, we worked on subcloning various merlin constructs, including those with S518 mutations, into adenoviral vectors. This will allow us to directly test the role of merlin in regulating the trafficking of ErbB2 in human vestibular schwannoma cells. Recently the Dept. of Defense and the Univ. of Iowa concurred that the project did not require IRB approval since it did not qualify as Human Subjects research and in the coming year we will be able to determine the extent to which replacement of merlin in human vestibular schwannoma cells regulates the trafficking of ErbB2 within the cell membrane.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 22, 2007
- Accession Number
- ADA479433
Entities
People
- Marlan Hansen
Organizations
- University of Iowa