Poster abstracts
Poster number 21 submitted by Wenfang Liu
Determining the Relationship Between P-bodies and Protein Quality Control: Defining the role of prefoldin
Wenfang Liu (MCDB program), Zachary Hurst (The Ohio State University), Shi Qian (MCDB program)
Abstract:
Eukaryotic cells contain a variety of cytoplasmic granules that each contain distinct sets of proteins and mRNAs. These ribonucleoprotein (RNP) structures lack a limiting membrane and can rapidly assemble in response to specific types of stress. The Processing-body (P-body) is a well-characterized RNP granule that contains translationally-repressed mRNAs as well as proteins involved in mRNA decay. However, the presence of P-bodies is not required for effective mRNA turnover and the physiological roles of these structures are still being worked out. Interestingly, our lab has found that there is an inverse relationship between the presence of P-bodies and the relative aggregation level of misfolded protein. These results have led us to propose that there is a relationship between P-bodies and the normal control of protein homeostasis in eukaryotic cells.
More recent work from our lab has identified a role for a heterohexameric chaperone complex, known as prefoldin, in P-body assembly. Specifically, the loss of any prefoldin subunit has been found to result in elevated P-body numbers in both wild-type cells and mutants that are typically defective for P-body formation. Prefoldin normally collaborates with the TRiC/CCT chaperonin complex to facilitate the folding of approximately 10% of newly-synthesized cytosolic proteins, including actin and tubulin. My project aims to identify the underlying mechanisms responsible for these effects on P-body formation and to determine whether there is a general connection between the systems regulating protein quality control and P-body assembly. The presented work will show that these effects of prefoldin are likely due to its role in the modulation of tubulin. Specifically, the misfolding of tubulin, and subsequent disruption of microtubules, was found to stimulate P-body formation. My ongoing efforts in the lab aim to define how this cytoskeletal network might influence RNP granule assembly.
References:
1. Thomas, M. G., Loschi, M., Desbats, M. A. & Boccaccio, G. L. RNA granules: The good, the bad and the ugly. Cell. Signal. 23, 324–334 (2011).
2. Luo, Y., Na, Z. & Slavoff, S. A. P-Bodies: Composition, Properties, and Functions. Biochemistry 57, 2424–2431 (2018).
3. Vainberg, I. E. et al. Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell 93, 863–873 (1998).
4. Gestaut, D. et al. The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic Interface Essential for Cellular Proteostasis. Cell 177, 751-765.e15 (2019).
5. Sweet, T. J., Boyer, B., Hu, W., Baker, K. E. & Coller, J. Microtubule disruption stimulates P-body formation. Rna 13, 493–502 (2007).
Keywords: RNP granules, P-bodies, Protein Quality Control, prefoldin