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.
| O'Neill, Ryan S; Schoborg, Todd A; Rusan, Nasser M (2018) Same but different: pleiotropy in centrosome-related microcephaly. Mol Biol Cell 29:241-246 |
| Lerit, Dorothy A; Shebelut, Conrad W; Lawlor, Kristen J et al. (2017) Germ Cell-less Promotes Centrosome Segregation to Induce Germ Cell Formation. Cell Rep 18:831-839 |
| Varadarajan, Ramya; Hammer, John A; Rusan, Nasser M (2017) A centrosomal scaffold shows some self-control. J Biol Chem 292:20410-20411 |
| Galletta, Brian J; Jacobs, Katherine C; Fagerstrom, Carey J et al. (2016) Asterless is required for centriole length control and sperm development. J Cell Biol 213:435-50 |
| Schoborg, Todd A; Rusan, Nasser M (2016) Taking Centrioles to the Elimination Round. Dev Cell 38:10-2 |
| Smyth, Jeremy T; Schoborg, Todd A; Bergman, Zane J et al. (2015) Proper symmetric and asymmetric endoplasmic reticulum partitioning requires astral microtubules. Open Biol 5: |
| Lerit, Dorothy A; Jordan, Holly A; Poulton, John S et al. (2015) Interphase centrosome organization by the PLP-Cnn scaffold is required for centrosome function. J Cell Biol 210:79-97 |
| Schoborg, Todd; Zajac, Allison L; Fagerstrom, Carey J et al. (2015) An Asp-CaM complex is required for centrosome-pole cohesion and centrosome inheritance in neural stem cells. J Cell Biol 211:987-98 |
| Pronobis, Mira I; Rusan, Nasser M; Peifer, Mark (2015) A novel GSK3-regulated APC:Axin interaction regulates Wnt signaling by driving a catalytic cycle of efficient ?catenin destruction. Elife 4:e08022 |
| Lerit, Dorothy A; Plevock, Karen M; Rusan, Nasser M (2014) Live imaging of Drosophila larval neuroblasts. J Vis Exp : |
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