Abstract
Vertebrate centrioles normally propagate through duplication, but in the absence of preexisting centrioles, de novo synthesis can occur. Consistently, centriole formation is thought to strictly rely on self-assembly, involving self-oligomerization of the centriolar protein SAS-6. Here, through reconstitution of de novo synthesis in human cells, we surprisingly found that normal looking centrioles capable of duplication and ciliation can arise in the absence of SAS-6 self-oligomerization. Moreover, whereas canonically duplicated centrioles always form correctly, de novo centrioles are prone to structural errors, even in the presence of SAS-6 self-oligomerization. These results indicate that centriole biogenesis does not strictly depend on SAS-6 self-assembly, and may require preexisting centrioles to ensure structural accuracy, fundamentally deviating from the current paradigm.
Highlights
Centrioles are microtubule-based, ninefold symmetrical structures essential for centrosome and cilia formation
We found that self-oligomerization of SAS-6, an activity proposed to drive cartwheel/centriole formation, is not essential for the structural assembly or shape determination of centrioles
De novo centriole formation can be sufficiently driven by the C-terminal half of SAS-6 lacking the self-oligomerization activity, fundamentally deviating from the current paradigm for centriole biogenesis
Summary
Centrioles are microtubule-based, ninefold symmetrical structures essential for centrosome and cilia formation. Centrioles are maintained in fixed numbers, and formed through canonical duplication depending on pre-existing (or mother) centrioles. In the absence of pre-existing centrioles, de novo synthesis can occur (Khodjakov et al, 2002). The number of centrioles formed through the de novo pathway is highly variable (Khodjakov et al, 2002; La Terra et al, 2005), providing an explanation for why canonical duplication dominates in dividing cells. In contrast to cycling cells, in post-mitotic cells such as multi-ciliated epithelia, the genes required for centriole assembly are highly up-regulated (Hoh et al, 2012) to produce large, variable numbers of centrioles prior to ciliogenesis, a process thought to primarily depend on de novo assembly (Dirksen, 1991). A recent study showed that the production of high quantities of centrioles in mouse multi-ciliated epithelia is driven by the pre-existing centriole rather than through de novo assembly (Al Jord et al, 2014), suggesting that the presence of pre-existing centrioles may have additional roles other than the number control for centriole biogenesis
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