The PCM1 protein was originally identified by virtue of its distinctcell cycle-dependent association with thecentrosome complex andmicrotubules. The protein appears to associate with the centrosome complex during the cell cycle. Dissociation occurs during mitosis when PCM1 is dispersed throughout the cell.Immunolabeling studies performed found that PCM1 was present in centriolar satellites and in electron dense granules between 70 and 100 nm in diameter. These were originally thought to be scattered only around the centrosomes, but further studies proved that PCM1 was also found throughout the cytoplasm.
PCM1 was shown to be essential for cell division because PCM1 antibodies cause cell-cycle arrest when microinjected into fertilized murine eggs. Targeting ofcentrin,pericentrin andninein was also dramatically reduced after PCM1 depletion using siRNA, overexpression of PCM1 deletion mutants and PCM1 antibody microinjection.[7] As a result of this depletion, the radial organization of the microtubules was found to be disrupted, but did not appear to affect microtubule nucleation.
PCM1 mRNA expression in themouse brain has been found to be highest in thehippocampus.[8] In humans it is expressed above the median level of central nervous system (CNS) expression in most parts of the brain.[9]
Mutations in thePCM1 gene have been shown to cause genetic susceptibility toschizophrenia. If an isoleucine amino acid change in PCM1 is inherited the risk of developing schizophrenia was found to be 68% in two independent samples from south England and Scotland. This means that it may now be possible to offer very limitedgenetic counselling to a small proportion of people with schizophrenia who are also carriers of this mutation.[10][11]
PCM1 forms a complex at thecentrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a link between aberrant PCM1 and the abnormal cortical development associated with the pathology of schizophrenia.[12]
^Li, Q; Hansen D; Killilea A; Joshi H C; Palazzo R E; Balczon R (February 2001). "Kendrin/pericentrin-B, a centrosome protein with homology to pericentrin that complexes with PCM-1".J. Cell Sci.114 (Pt 4):797–809.doi:10.1242/jcs.114.4.797.ISSN0021-9533.PMID11171385.
Ohata H, Fujiwara Y, Koyama K, Nakamura Y (1995). "Mapping of the human autoantigen pericentriolar material 1 (PCM1) gene to chromosome 8p21.3-p22".Genomics.24 (2):404–6.doi:10.1006/geno.1994.1640.PMID7698772.
Li Q, Hansen D, Killilea A, et al. (2001). "Kendrin/pericentrin-B, a centrosome protein with homology to pericentrin that complexes with PCM-1".J. Cell Sci.114 (Pt 4):797–809.doi:10.1242/jcs.114.4.797.PMID11171385.
Brill LM, Salomon AR, Ficarro SB, et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry".Anal. Chem.76 (10):2763–72.doi:10.1021/ac035352d.PMID15144186.
