This presentation is accessible only to the Illinois State University community.
- Off-Campus ISU Users: To download this item, click the "Off-Campus Download" button below. You will be prompted to log in with your ISU ULID and password.
Download Presentation (303 KB)
Cilia are cellular protrusions that are important for many actionsin the body. For instance, motile ciliary structures clear material from the upper airways via directional mucus flow across the respiratory epithelium. The assembly of cilia is coordinated with the cell cycle and is known as ciliogenesis. Intraflagellar transport (IFT) is essential for ciliogenesis and aids the maintenance and function of cilia. During this transport process, cellular cargoes are shuttled along the microtubules of the axoneme: Kinesin-2 (KIF3A/KIF3B/KAP) drives transport to the tip of the cilium and dynein-2 motors drive transport back to the cell body. Heterotrimeric kinesin-2 belongs to the super family of the kinesin motors and next to IFT also drives membrane organelle transport in the cytoplasm. Proteins generally undergo post-translational modifications like phosphorylation, glycosylation, ubiquitination, and methylation. These modificationsincrease the functional diversity of proteins and regulate their activity. Misregulation of any of these modifications can result in unphysiological functionality of the target protein. For example, Chaya and colleagues (EMBO J., 2014) generated a KIF3A mutant in which all eight potential serine and threonine phosphorylation sites in the tail domain of the protein were removed and this mutant was unable to drive ciliogenesis. These results demonstrate that KIF3A phosphorylation is important for the function of KIF3A. However, it is unknown which of the exact phosphorylation sites is necessary to drive ciliogenesis. I hypothesize that dephosphorylation of a specific residue will stop IFT, outlining my aim to delineate the function of specific phosphorylation site in the tail of KIF3A. Kinesins have high medical relevance, but for technical reasons, there are very few drugs that directly affect the activity of specific kinesins. My effort to contribute to the understanding of the effects of phosphorylation on kinesin-mediated processes on a molecular level may thus open new avenues for drug discovery and therapeutical intervention.
Fasawe, Ayoola, "Assessing The Effects Of Phosphorylation On The Function And Activity Of The Kinesin-2 Motor" (2021). Biology. 25.