Mouse Odf2 localizes to centrosomes and basal bodies in adult tissues and to the photoreceptor primary cilium

Odf2 (outer dense fiber 2) is the major protein of the cytoskeleton of the sperm tail. In somatic cells, it is a component of the centrosome in which it is located in the appendages of the mother centriole. Additionally, as shown previously by forced expression in cultured cells, Odf2 localizes to centrioles, basal bodies, and primary cilia, which are all structurally and functionally interconnected. The importance of Odf2 has become obvious by the absence of primary cilia in Odf2-deficient cells and by the embryonic lethality of the Odf2 gene trap insertional mouse. However, nothing is known about the endogenous localization of Odf2 in the tissues of adult mice. We show here that Odf2 protein localizes to centrosomes, to photoreceptor primary cilia, and to basal bodies of ciliated cells of the respiratory epithelium and of the kidney. Our results thus suggest that Odf2 contributes to assorted ciliopathies

Diverse system stresses: common mechanisms of chromosome fragmentation

Chromosome fragmentation (C-Frag) is a newly identified MCD (mitotic cell death), distinct from apoptosis and MC (mitotic catastrophe). As different molecular mechanisms can induce C-Frag, we hypothesize that the general mechanism of its induction is a system response to cellular stress. A clear link between C-Frag and diverse system stresses generated from an array of molecular mechanisms is shown. Centrosome amplification, which is also linked to diverse mechanisms of stress, is shown to occur in association with C-Frag. This led to a new model showing that diverse stresses induce common, MCD. Specifically, different cellular stresses target the integral chromosomal machinery, leading to system instability and triggering of MCD by C-Frag. This model of stress-induced cell death is also applicable to other types of cell death. The current study solves the previously confusing relationship between the diverse molecular mechanisms of chromosome pulverization, suggesting that incomplete C-Frag could serve as the initial event responsible for forms of genome chaos including chromothripsis. In addition, multiple cell death types are shown to coexist with C-Frag and it is more dominant than apoptosis at lower drug concentrations. Together, this study suggests that cell death is a diverse group of highly heterogeneous events that are linked to stress-induced system instability and evolutionary potential

Gene ontology analysis of the centrosome proteomes of Drosophila and human

The centrosome is a complex cell organelle in higher eukaryotic cells that functions in microtubule organization and is integrated into major cellular signaling pathways.1–3 For example, a tight link exists between cell cycle regulation and centrosome duplication, as centrosome numbers must be precisely controlled to ensure high fidelity of chromosome segregation.4 The analysis of the centrosome's protein composition provides the opportunity for a better understanding of centrosome function and to identify possible links to cellular signaling pathways.5,6 Our proteomics study of the Drosophila centrosome recently identified 251 centrosome candidate proteins that we subsequently characterized by RNAi in Drosophila SL2 cells and classified according to their function in centrosome duplication/segregation, structure maintenance and cell cycle regulation.7 Interestingly, functional characterization of their human orthologous proteins revealed the highest functional conservation in the process of centrosome duplication and separation. To analyze functional and biochemical interdependencies further, we carried out an analysis of the gene ontology (GO) annotation of the identified Drosophila centrosome proteins, as well as of the human centrosome proteome.5 The GO analysis of the group of proteins that did not show a centrosome, chromosome segregation or cell cycle related phenotype in our RNAi assays suggests that these molecules may constitute linker proteins to other cellular signaling pathways. Furthermore, the results of our GO analysis of components of the human and of the Drosophila centrosome reflect the somatic and embryonic origin, respectively, of the isolated centrosomes, implicating the Drosophila centrosome proteins in developmental signaling and cell differentiation