PCM1

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Pericentriolar material 1
Identifiers
Symbols PCM1 ; PTC4
External IDs OMIM600299 MGI1277958 HomoloGene4518 GeneCards: PCM1 Gene
RNA expression pattern
PBB GE PCM1 202174 s at tn.png
PBB GE PCM1 209996 x at tn.png
PBB GE PCM1 209997 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5108 18536
Ensembl ENSG00000078674 ENSMUSG00000031592
UniProt Q15154 Q9R0L6
RefSeq (mRNA) NM_006197 NM_023662
RefSeq (protein) NP_006188 NP_076151
Location (UCSC) Chr 8:
17.78 – 17.89 Mb
Chr 8:
41.24 – 41.33 Mb
PubMed search [1] [2]

Pericentriolar material 1, also known as PCM1, is a protein which in humans is encoded by the PCM1 gene.[1][2][3]

Function[edit]

The PCM1 protein was originally identified by virtue of its distinct cell cycle-dependent association with the centrosome complex and microtubules. 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 of centrin, pericentrin and ninein was also dramatically reduced after PCM1 depletion using siRNA, overexpression of PCM1 deletion mutants and PCM1 antibody microinjection.[4] As a result of this depletion, the radial organization of the microtubules was found to be disrupted, but did not appear to effect microtubule nucleation.

Structure[edit]

PCM1 has four known transcripts, the longest of which has 39 exons. The open reading frame of PCM1 encodes a protein of 2024 amino acids. The protein contains coiled coil regions between areas of low complexity as well as an adenosine triphosphate (ATP) / GTPase domain, a nuclear localization domain and a eukaryotic molybdopterin domain. The eukaryotic molybdopterin binding domain is currently found in only five other human genes, xanthine dehydrogenase, sulfite oxidase (mitochondrial precursor), aldehyde oxidase, erythropoietin receptor precursor and the ATPbinding cassette, sub-family A, member 2 (ABCA2).

Tissue distribution[edit]

PCM1 mRNA expression in the mouse brain has been found to be highest in the hippocampus.[5] In humans it is expressed above the median level of central nervous system (CNS) expression in most parts of the brain.[6]

Clinical significance[edit]

Mutations in the PCM1 gene have been shown to cause genetic susceptibility to schizophrenia. 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 limited genetic counselling to a small proportion of people with schizophrenia who are also carriers of this mutation.[7][8]

PCM1 forms a complex at the centrosome 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.[9]

Interactions[edit]

PCM1 has been shown to interact with PCNT.[10]

References[edit]

  1. ^ "Entrez Gene: PCM1 pericentriolar material 1". 
  2. ^ Balczon R, Bao L, Zimmer WE (March 1994). "PCM-1, A 228-kD centrosome autoantigen with a distinct cell cycle distribution". J. Cell Biol. 124 (5): 783–93. doi:10.1083/jcb.124.5.783. PMC 2119948. PMID 8120099. 
  3. ^ Hames RS, Crookes RE, Straatman KR, Merdes A, Hayes MJ, Faragher AJ, Fry AM (April 2005). "Dynamic Recruitment of Nek2 Kinase to the Centrosome Involves Microtubules, PCM-1, and Localized Proteasomal Degradation". Mol. Biol. Cell 16 (4): 1711–24. doi:10.1091/mbc.E04-08-0688. PMC 1073654. PMID 15659651. 
  4. ^ Dammermann, A.; Merdes, A. (2002). "Assembly of centrosomal proteins and microtubule organization depends on PCM-1". The Journal of Cell Biology 159 (2): 255–266. doi:10.1083/jcb.200204023. PMC 2173044. PMID 12403812.  edit
  5. ^ "Gene Expression Summary for Pcm1; pericentriolar material 1". Allen Institute for Brain Science. Retrieved 2009-04-30. 
  6. ^ "PCM1, Probe set 202174_s_at". BioGPS - your Gene Portal System. Retrieved 2009-04-30. 
  7. ^ Datta SR, McQuillin A, Rizig M, Blaveri E, Thirumalai S, Kalsi G, Lawrence J, Bass NJ, Puri V, Choudhury K, Pimm J, Crombie C, Fraser G, Walker N, Curtis D, Zvelebil M, Pereira A, Kandaswamy R, St Clair D, Gurling HM (December 2008). "A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia". Mol. Psychiatry 15 (6): 615–28. doi:10.1038/mp.2008.128. PMID 19048012. 
  8. ^ Gurling HM, Critchley H, Datta SR, McQuillin A, Blaveri E, Thirumalai S, Pimm J, Krasucki R, Kalsi G, Quested D, Lawrence J, Bass N, Choudhury K, Puri V, O'Daly O, Curtis D, Blackwood D, Muir W, Malhotra AK, Buchanan RW, Good CD, Frackowiak RS, Dolan RJ (August 2006). "Genetic Association and Brain Morphology Studies and the Chromosome 8p22 Pericentriolar Material 1 (PCM1) Gene in Susceptibility to Schizophrenia". Arch. Gen. Psychiatry 63 (8): 844–54. doi:10.1001/archpsyc.63.8.844. PMC 2634866. PMID 16894060. 
  9. ^ Kamiya A, Tan PL, Kubo K, Engelhard C, Ishizuka K, Kubo A, Tsukita S, Pulver AE, Nakajima K, Cascella NG, Katsanis N, Sawa A (September 2008). "PCM1 is recruited to the centrosome by the cooperative action of DISC1 and BBS4 and is a candidate for psychiatric illness". Arch. Gen. Psychiatry 65 (9): 996–1006. doi:10.1001/archpsyc.65.9.996. PMC 2727928. PMID 18762586. 
  10. ^ 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. (England) 114 (Pt 4): 797–809. ISSN 0021-9533. PMID 11171385. 

Further reading[edit]