Structural-functional characterization of Plp

Authors

• R Varadarajan
• K Plevock
• CJ Fagerstrom
• NM Rusan

Abstract

Centrosomes are the major microtubule organizing centers in most eukaryotes. A typical centrosome consists of a pair of centrioles encircled by a proteinaceous pericentriolar material (PCM). Centrosome maturation is a key cell cycle processes that facilitates recruitment of PCM proteins to the centrioles thereby enable centrosome-driven functions including microtubule nucleation. Mutations in PCM proteins (Pericentrin and Centrosomin) are associated with many human genetic disorders, including cancer and ciliopathies. Drosophila is an excellent model system to study the centrosome and diseases that are related to their dysfunction. Here, we focus on understanding the molecular mechanisms underlying PCM recruitment and microtubules nucleation. Pericentrin like protein (Plp) is a centrosome protein shown to mediate PCM recruitment, however, its interdependent interaction with other essential PCM components such as Asl, Sas4, Spd2 and CNN remains unclear. To investigate the precise role of Plp during maturation, we performed a structure-function analysis using by generating Plp protein truncation and characterized its function in vivo. We found that the C terminal region of Plp contains a promoting signal for PCM recruitment, while the N terminal region contains an inhibitory signal encoded within amino acids 649-933 of Plp. Interestingly, we found direct binding between the inhibitory and promoting regions (aa 2538-2747) of Plp, suggesting a sophisticated autoinhibition mechanism at play. Our working model is that Plp resides in a closed/inhibited conformation in interphase to prevent PCM recruitment. In mitosis, this autoinhibition is relieved and the C-terminus is then allowed to recruit other PCM components. We are now focusing on identifying the molecular interactions between Plp and other PCM protein, which may further explain the role of Plp in PCM recruitment and microtubules nucleation.

Scientific Focus Area: Cell Biology

This page was last updated on Friday, March 26, 2021