Abstract
A long-standing mystery in the centrosome field pertains to the origin of asymmetry within the organelle. The removal of daughter centriole-specific/enriched proteins (DCPs) and acquisition of distal appendages on the future mother centriole are two important steps in the generation of asymmetry. We find that DCPs are recruited sequentially, and their removal is abolished in cells lacking Talpid3 or C2CD3. We show that removal of certain DCPs constitutes another level of control for distal appendage (DA) assembly. Remarkably, we also find that Talpid3 forms a distal centriolar multi-functional hub that coordinates the removal of specific DCPs, DA assembly, and recruitment of ciliary vesicles through distinct regions mutated in ciliopathies. Finally, we show that Talpid3, C2CD3, and OFD1 differentially regulate the assembly of sub-distal appendages, the CEP350/FOP/CEP19 module, centriolar satellites, and actin networks. Our work extends the spatial and functional understanding of proteins that control organelle maturation and asymmetry, ciliogenesis, and human disease.
Highlights
A long-standing mystery in the centrosome field pertains to the origin of asymmetry within the organelle
Consistent with the role of distal appendage (DA) in multiple processes, we found that intraflagellar transport (IFT) protein (IFT88 and IFT140) localization, TTBK2 recruitment, and CP110 removal were abrogated in Talpid3−/− cells
In this study, we identified Talpid[3] and C2CD3 as critical regulators of daughter centriole-specific/enriched proteins (DCPs) removal and revealed that removal of certain DCPs constitutes another level of control for DA assembly
Summary
A long-standing mystery in the centrosome field pertains to the origin of asymmetry within the organelle. The constellation of DA and SDA proteins have been identified and localized with ever-increasing precision, the relationship between the assembly of these structures, removal of DCPs, and mother centriole maturation—the basis of asymmetry within the organelle—remains largely uncharacterized. To this end, it is attractive to speculate that mother and daughter centriole components display antagonistic relationships to suppress or promote their respective identities. The location and function of Talpid[3], C2CD3, and OFD1 are coordinated and, in some cases, interdependent, we found that each protein exhibits distinct roles in regulating the actin network, CS organization, removal of DCPs, and assembly of appendages. Our data suggest potential mechanisms to explain how Talpid[3] mutations found in JBTS contribute to disease phenotypes
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