Disease relevance of Centrioles

• Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles [1].
• Sp6, a fibrosarcoma, has abundant virus-like particles in the cytoplasm, very often associated with centrioles or basal bodies of a cilium [2].
• In two adenomas, instead of the honeycomb Golgi complex, another unique alteration of the Golgi apparatus was encountered, comprising transformation of Golgi complex into a tripartite cloverleaflike structure with a pair of centrioles at its base [3].

High impact information on Centrioles

• Like tubulin, SAS-4 is incorporated into centrioles during their duplication and remains stably associated thereafter [4].
• Electron microscopic immunocytochemistry localized this antigen in dense pericentriolar material (PCM) surrounding the centrioles [5].
• In six dd4 cells subjected to serial sectioning centrioles were missing from one of the two poles [6].
• Odf2-deficient mother centrioles lack distal/subdistal appendages and the ability to generate primary cilia [7].
• The Polo kinase Plk4 functions in centriole duplication [8].

Biological context of Centrioles

• Results suggest PCM can exist, disperse, and reorganize during the cell cycle independently of the centriole, and its distribution in the embryo differs in cells having different fates [5].
• CMG-1 was present in particles along primary cilia of HUVEC at interphase and around the oldest basal body/centriole at interphase and mitosis [9].
• The progress of centrioles through these stages was determined in synchronous populations of cells starting from S or M phase, in cells inhibited in DNA synthesis by addition of thymidine, and in cytoplasts [10].
• In both cases, the electron-opaque material associated with these microtubule organizing centers (MTOC's) can be removed by RNAse digestion and cold perchloric acid (PCA) extraction under conditions which leave the spindle microtubules (Mts) centrioles, and kinetochores intact [11].
• Furthermore, inhibition of centriole duplication by centrobin depletion led to impaired cytokinesis [12].

Anatomical context of Centrioles

• Epsilon-tubulin is required for centriole duplication and microtubule organization [13].
• Outer dense fibre 2 (Odf2; also known as cenexin) was initially identified as a main component of the sperm tail cytoskeleton, but was later shown to be a general scaffold protein that is specifically localized at the distal/subdistal appendages of mother centrioles [7].
• Immunofluorescence with an anticentrosome serum and EM demonstrated that the MTOCs in cycloheximide-treated cells were typical centrosomes, containing centrioles and pericentriolar material [14].
• In contrast, the antigen was not detected in preparations of soluble, cytoplasmic tubulin, which would not have contained tubulin from stable microtubule arrays such as centrioles, from unfertilized sea urchin eggs, Drosophila embryos, and HeLa cells [15].
• By following the intracellular processing of recycling transferrin receptors and the selective sorting of a-2 macroglobulin in chick embryo fibroblasts, we have shown that the concentration of 60 nm diam tubules which surrounds the centrioles represents a distal compartment on the recycling pathway [16].

Associations of Centrioles with chemical compounds

• Although clouds of PCM consistently form even when microtubules are completely disassembled by nocodazole, the centrioles are not assembled under these conditions [17].
• Although the precise identity of the immunoreactive steroid substance has not yet been established, it seems noteworthy that exogenous steroids can be vitally concentrated by centrioles, perhaps by exchange with steroids already present at this level [18].
• When these cells were exposed to microtubule reassembly buffer containing Triton X-100 and bovine brain tubulin at 37 degrees C, numerous microtubules were reassembled at all kinetochores of metaphase chromosomes and in association with centriole pairs [19].
• Its partial localization to centrioles and basal bodies raises the possibility that purine compounds are involved in centriole replication and/or in the regulation of microtubule assembly in vivo [20].
• We also demonstrate that PTN stimulates translocation of phosphoserine 713 and 726 beta-adducin either to nuclei, where it associates with nuclear chromatin and with centrioles of dividing cells, or to a membrane-associated site, depending on the phase of cell growth [21].

Gene context of Centrioles

• Further, we show that depletion of NEDD1 inhibits centriole duplication, as does depletion of gamma-tubulin [22].
• RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal bodies and interacts with nucleophosmin [23].
• As shown by immunoelectron microscopy, Cep170 associates with subdistal appendages, typical of the mature mother centriole [24].
• Similar to BRCA1-deficient mouse embryonic fibroblasts, the tumor cells contained supernumerary functional centrosomes with intact centrioles whose presence results in multipolar mitoses and aneuploidy [25].
• We report here that HPV E7-induced abnormal centriole duplication is specifically abrogated by a small molecule CDK inhibitor, indirubin-3'-oxime (IO), but not a kinase-inactive derivative [26].

Analytical, diagnostic and therapeutic context of Centrioles

• Electron microscopy indicates not only that the poles of dd4 cells have irregular amounts of pericentriolar material, but also that they can have abnormal centrioles [6].
• The localization and migration of centriole duplexes have been studied in PtK2 cells by indirect immunofluorescence microscopy using specific tubulin antibodies [27].
• Light microscopy following silver staining of spermatocytes of German and Madagascar hissing cockroaches demonstrated: (1) the localization of a kinetochore in each autosomal synaptonemal complex during pachytene, and (2) visualization of centrioles in different stages of meiotic prophase [28].

References