Abstract
Centrosomes, the main microtubule organizing centers (MTOCs) of metazoan cells, contain an older "mother" and a younger "daughter" centriole. Stem cells either inherit the mother or daughter-centriole-containing centrosome, providing a possible mechanism for biased delivery of cell fate determinants. However, the mechanisms regulating centrosome asymmetry and biased centrosome segregation are unclear. Using 3D-structured illumination microscopy (3D-SIM) and live-cell imaging, we show in fly neural stem cells (neuroblasts) that the mitotic kinase Polo and its centriolar protein substrate Centrobin (Cnb) accumulate on the daughter centriole during mitosis, thereby generating molecularly distinct mother and daughter centrioles before interphase. Cnb's asymmetric localization, potentially involving a direct relocalization mechanism, is regulated by Polo-mediated phosphorylation, whereas Polo's daughter centriole enrichment requires both Wdr62 and Cnb. Based on optogenetic protein mislocalization experiments, we propose that the establishment of centriole asymmetry in mitosis primes biased interphase MTOC activity, necessary for correct spindle orientation.
Highlights
Centrosomes consist of a pair of centrioles, embedded in structured layers of pericentriolar material (PCM) [1]
Neuroblast centriole duplication starts in interphase and completes in mitosis To determine the onset of centrosome asymmetry establishment in larval neuroblast, we first investigated the centriole replication cycle
Centrosome asymmetry has previously been described to occur in asymmetrically dividing Drosophila neural stem cells, manifested in biased interphase microtubule organizing center (MTOC) activity and asymmetric localization of the centrosomal proteins Cnb, PCNT-like protein (Plp), and Polo [8,19,20,21,22] and PCM proteins like Centrosomin [9]
Summary
Centrosomes consist of a pair of centrioles, embedded in structured layers of pericentriolar material (PCM) [1]. The active interphase MTOC contains the daughter centriole from the previous cell cycle, identifiable with the orthologue of the human daughtercentriole-specific protein Cnb (Cnb+) [8]. This biased MTOC activity is regulated by the mitotic kinase Polo (Plk in vertebrates). Several centrosomal proteins have been described to be enriched on either the mother or daughter centrosome in Drosophila interphase neuroblasts [8,20,23] or human cells [24,25,26], it is unknown when and how centrosomes acquire their unique molecular identity to determine biased MTOC activity and correct spindle orientation. We further show that priming centrosome asymmetry in mitosis is necessary to establish molecularly distinct centrosomes, asymmetric MTOC activity and centrosome positioning
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
