Disease relevance of Pcm1

• In control CTLs, not treated with taxol, a mild hyperthermia treatment (42 degrees C, 30 min) results in an aggregation of the pericentriolar material, a loss of MTOC orientation, an inhibition of cytolytic activity, and a disorganization of the microtubule system [Knox et al.: Exp. Cell Res. 194:275-283, 1991] [1].

High impact information on Pcm1

• Centrosome development in early mouse embryos as defined by an autoantibody against pericentriolar material [2].
• During this time PCM was found assembled at a single locus in the cell and exclusively in mitotic cells; it was not observable in interphase cells [2].
• Using a GFP fusion protein with PCM-1, we found that PCM-1-containing centriolar satellites moved along microtubules toward their minus ends, i.e., toward centrosomes, in live cells, as well as in vitro reconstituted asters [3].
• These findings suggested that centriolar satellites and fibrous granules are identical novel nonmembranous organelles containing PCM-1, which may play some important role(s) in centriolar replication [3].
• Next, to understand the relationship between centriolar satellites and centriolar replication, we examined the expression and subcellular localization of PCM-1 in ciliated epithelial cells during ciliogenesis [3].

Biological context of Pcm1

• The distribution of microtubules and microtubule organizing centers (MTOCs) during the development of cell polarity in eight-cell mouse blastomeres was studied by immunofluorescence and immunoelectron microscopy using monoclonal anti-tubulin antibodies and an anti-pericentriolar material (PCM) serum [4].
• More prolonged exposure to DMSO leads to progressive disassembly of the spindle, and as a result dispersal of the chromosomes and polar PCM foci occurs, and tubulin polymerization becomes confined to PCM-organized asters [5].
• The analysis of ultrathin sections through spindles revealed large amounts of pericentriolar material at the spindles poles, in prometaphase through anaphase [6].
• During gametogenesis, the spermatozoon retains its proximal centriole while losing most of the PCM, whereas the oocyte degenerates centrioles while retaining centrosomal proteins [7].
• Since the mature oocyte at metaphase II has no centrioles at spindly poles, this centriole was most likely derived from the sperm, which has a single proximal centriole associated with pericentriolar material in its neck region, like most mammalian sperm [8].

Anatomical context of Pcm1

• Immunolabeling revealed that PCM-1 was not a pericentriolar material protein, but a specific component of centriolar satellites, morphologically characterized as electron-dense granules, approximately 70-100 nm in diameter, scattered around centrosomes [3].
• About 70-80% of the centrosomes derived from nonirradiated cells were composed of a pair of centrioles and pericentriolar material, which initiated greater than 100 microtubules [9].
• In early eight-cell blastomeres microtubules were found mainly around the nucleus and in the cell cortex, whereas PCM foci were observed dispersed in the cytoplasm [4].
• These cells have no centrioles, and their multiple microtubule-organizing centers (MTOCs) are composed of foci of pericentriolar material [3,4] [10].
• Centrosomal reorganization in the cells in question, outer pillar cells of the organ of Corti, indicates that its pericentriolar material becomes intimately associated with the plasma membrane at the two nucleating sites [11].

Other interactions of Pcm1

• EM suggests that this disorganization of the microtubules may result from an aggregation of the pericentriolar material [12].

Analytical, diagnostic and therapeutic context of Pcm1

• When ciliogenesis was induced in mouse nasal respiratory epithelial cells, PCM-1 immunofluorescence was markedly elevated at the apical cytoplasm [3].
• The MAP1B-related antigen is localized to the pericentriolar material as revealed by immunoelectron microscopy [13].
• Electron microscopy showed a spheroidal, filamentous structure with at least some filaments closely associated with the pericentriolar material (PCM) [14].

References