For asymmetric divisions to proceed properly, stem cells must accomplish the following: A) establish proper polarity, B) build a functional mitotic spindle using centrosomes that steer and anchor it, and C) properly align the spindle along a defined polarity axis using forces generated by astral MTs-cortical interactions. If executed properly, stem cells divide asymmetrically to produce a differentiating daughter cell. However, defects in this process lead to missegregation of cell fate determinants. Over the past year, we have investigated how centrosomes play critical roles in this process. We generated the necessary tools to identify any unique aspects of centrosome behavior during stem cell division. Both our fixed and live analysis of the protein Pericentrin show that it was enriched on the basal centrosome, a property that it does not share with any other centrosome protein. Our detailed analysis of Pericentrin in these cells has shown that it serves as a negative regulator of centrosome activity. This makes Pericentrin the only known proteins to shield the centrosome from the recruitment of the master regulator Polo. When perturbed, centrosome inheritance to the stem cell and progeny is significantly disrupted. Current work is focused on identifying and understanding proteins that fall upstream and downstream of Periceintrin this critical pathway.
|Lerit, Dorothy A; Smyth, Jeremy T; Rusan, Nasser M (2013) Organelle asymmetry for proper fitness, function, and fate. Chromosome Res 21:271-86|