Neuronal L-type calcium channels are regulated by FMR1 and SPOPL
Abstract/Contents
- Abstract
- Voltage-gated calcium channels (VGCCs) regulate cellular excitability, differentiation and connectivity. The L-type Ca2+ channel (LTC) CaV1.2 is the most abundant VGCC in the brain, and mis-regulation of LTCs has been linked to bipolar disorder, schizophrenia and autism spectrum disorders. However, how LTC activity is regulated in vivo is incompletely understood. Here we describe a new approach using a high throughput genome-wide screen in Drosophila to identify modulators of CaV1.2 activity. This screen uncovered two novel CaV1.2 regulating proteins, Fragile X Mental Retardation 1 (FMR1) and Speckle-type POZ protein-like (SPOPL). Using biochemistry, calcium-imaging, and electrophysiology in mammalian neurons, we show that FMR1 binds directly to CaV1.2 and regulates its surface expression, while SPOPL alters ubiquitination and electrical properties of the channel. These results reveal new regulatory pathways controlling CaV1.2 activity, and describe a generalizable approach to identifying modulators of LTC function in vivo.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2013 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Wen, Susanna |
|---|---|
| Associated with | Stanford University, Department of Chemical and Systems Biology. |
| Primary advisor | Dolmetsch, Ricardo E |
| Thesis advisor | Dolmetsch, Ricardo E |
| Thesis advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Thesis advisor | Elias, Joshua |
| Thesis advisor | Mochly-Rosen, Daria |
| Advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Advisor | Elias, Joshua |
| Advisor | Mochly-Rosen, Daria |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Susanna Wen. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Ph.D. Stanford University 2013 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2013 by Susanna Wen
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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