Figure 4

Modes of centriole over production. We propose that hMps1 and Cetn2 cooperate to generate centriole overproduction by two distinct mechanisms. First, in Mps1^Δ12/13-induced centriole overproduction, hMps1^Δ12/13 promotes the assembly of multiple hSas6 containing precursors (analogous to the proposed hSas6-containing intermediate in procentriole assembly described in Figure 3). As in the canonical centriole assembly pathway, we assume that hMps1 is required for the remodeling of these precursors into cartwheels, onto which procentrioles are assembled. The figure reflects the possibility that not all of the precursors become cartwheels, based on the observation that the percentage of cells with excess hSas6 foci is greater than the percentage of cells with excess γ-Tubulin or CP110 foci [28]. Second, hMps1 is also required for initiation of Cetn2-induced centriole overproduction. We propose that overexpression of wild type Cetn2 leads to the assembly of Cetn2-containing precursors that organize distal centriole modules in a top-down fashion that is independent of hSas6. Because Mps1 is required for the initiation of these structures, we cannot assess a role for Mps1 in their maturation. However, while the initiation of these structures is hSas6-independent, some aspects of their maturation require hSas6, as suggested by the observation that a subset of centriole proteins are not recruited to these structures in the absence of hSas6 [28]. Because these structures recruit hSas6, it is possible that they can recruit cartwheels (indicated by a question mark). Structures and colors are as in Figure 3.