Centrioles are cylindrical microtubule-based structures, constituting the core of centrosomes — the major microtubule-organizing centres in most animal cells. Centrioles are typically found in pairs, comprising a mother centriole accompanied by its daughter, which is acquired in the process of duplication. Following subsequent mitosis, the daughter reaches full maturity and becomes a new, competent for duplication mother. The process of centriole duplication involves multiple proteins, but how they act together to initiate duplication and then extend the new centriole remains elusive. To better understand this fundamental process, Fu et al. explored in their recent study how the conversion from daughter to duplication-competent mother centriole is achieved.
The authors utilized super-resolution microscopy on cultured Drosophila melanogaster cells to investigate the localization of proteins known for their involvement during centriole duplication. This revealed that three proteins: Cep135 (also known as Bld10), Ana1 (Anastral spindle 1; vertebrate Cep295) and Asl (Asterless; vertebrate Cep152) were sequentially recruited to daughter centrioles as they matured from late interphase through mitosis. These proteins displayed notable localization patterns, forming partially overlapping, concentric circles within the daughter centriole cylinder, with Cep135 most centrally and Asl most peripherally located.
“Asl is recruited to the centriole via a linker provided by Ana1, which in turn interacts with Cep135”
Detailed biochemical investigations, as well as experiments in cells, revealed the existence of a network, in which Asl is recruited to the centriole via a linker provided by Ana1, which in turn interacts with Cep135 to localize to the centriole. Correct expression of all three proteins was found to be necessary for unperturbed centriole duplication, thus illustrating the functional importance of this network. Notably, the authors revealed that a similar network also operates in mammalian cells, thus indicating that it represents a conserved mechanism of licensing daughter centrioles for duplication.
In summary, Cep135, Ana1 and Asl are sequentially recruited to the daughter centriole during its maturation, forming a molecular network. As Asl serves as a scaffold for the recruitment of Plk4 (Polo-like kinase 4) — which is the master regulator of the centriole duplication pathway — this network allows the conversion of a daughter to a mother centriole, which is fully competent for duplication. It will be important to investigate how this molecular cascade of interactions cooperates with other components of the complex centriole duplication machinery.
Fu, J. et al. Conserved molecular interactions in centriole-to-centrosome conversion. Nat. Cell Biol. http://dx.doi.org/10.1038/ncb3274 (2015)
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Annual Review of Cell and Developmental Biology (2017)