Hegde explains that although the protein localization system usually operates accurately, it does sometimes fail. This can be due to genetic mutations, stress within an organelle, or just intrinsic inefficiencies that accompany any complex process. As a graduate student, Hegde used a cell-free in vitro system to study the translocation of prion protein into the ER. He found that a small amount of prion protein did not completely cross the ER membrane as expected, but remained in a transmembrane form. Worried that this was an artifact of the in vitro system, he designed experiments in mice to see what the effect of an increase in mislocalized, transmembrane prion protein would be. He found a striking result – even a small increase in the amount of transmembrane prion protein caused increased neurodegeneration in mice. It turns out that incomplete translocation is not unique to prion protein. Hegde tells us how, as an independent investigator, his lab went on to investigate why this happens and how the cell monitors and degrades proteins that are not properly localized.
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Protein Localization Inside Cells
How does the cell regulate protein localization to be sure that proteins end up where they should? Manu Hegde reviews experiments that answer this question. (Talk recorded in April 2017)
- Part 1: Compartmentalization of Proteins Inside CellsAudience:
- Student
- Researcher
- Educators of H. School / Intro Undergrad
- Educators of Adv. Undergrad / Grad
Duration: 00:43:08 - Part 2: Quality Control of Protein LocalizationAudience:
- Researcher
- Educators of Adv. Undergrad / Grad
Duration: 00:34:09 - Part 3: Recognition of Protein Localization SignalsAudience:
- Researcher
- Educators of Adv. Undergrad / Grad
Duration: 00:46:27