The centrosome, which plays a central role as the main microtubule (MT)-organizing center for animal cell division, is a membraneless organelle composed of a pair of orthogonally arranged MT-derived apparatus, called centrioles, and the surrounding pericentriolar material (PCM). In various eukaryotic organisms, PCM proteins are concentrically arranged around a centriole in a highly organized manner. Based on this observation, proper positioning and organization of PCM proteins may be important for promoting different cellular processes in a spatially regulated manner. Not surprisingly, aberrations in the function of PCM scaffolds are associated with many human diseases including cancer, microcephaly, ciliopathy, and dwarfism. At present, how this membraneless cellular architecture is assembled and how the centrosomal scaffold proteins display a cylindrical pattern of localization around a centriole remain unknown. The formation of a higher-order structure requires unusual biochemical and biophysical properties that allow a building-block molecule to establish the boundary of an assembled structure in an open cytosolic environment. Recent studies showed that a C. elegans centrosomal scaffold, Spd5, homomerizes to form a network-like assembly through its phase-separating ability. In addition, the D. melanogaster Centrosomin (Cnn) appears to form a network-like assembly that does not undergo dynamic turnover. However, both Spd5 and Cnn do not appear to form an organized higher-order architecture with a distinguishable morphology. We found that two of the human PCM scaffolds, Cep63 and Cep152, cooperate to generate a higher-order cylindrical self-assembly capable of recruiting their downstream components, such as Plk4, a key regulator of centriole duplication. Cooperative self-assembly of a three-dimensional cylindrical architecture by two distinct intracellular proteins is unprecedented. Since Cep152 is thought to function as a licensing factor for Plk4-mediated centriole biogenesis , investigating the mechanism of how Cep152 functions in conjunction with Cep63 to self-assemble a new structural entity will be important to comprehend the centrosomal architecture critically required for Plk4-dependent centriole duplication.
NIH ExPorter
NIH ExPorter