Pericentriolar material 1, also known as PCM1, is a protein which in humans is encoded by the PCM1 gene. [4] [5] [6]
Pericentriolar material 1, also known as PCM1, is a protein which in humans is encoded by the PCM1 gene. [4] [5] [6]
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. [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 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).
PCM1 mRNA expression in the mouse brain has been found to be highest in the hippocampus. [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 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. [10] [11]
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. [12]
In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progression. The centrosome provides structure for the cell. The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes and therefore use other structures to organize their microtubules. Although the centrosome has a key role in efficient mitosis in animal cells, it is not essential in certain fly and flatworm species.
In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.
Disrupted in schizophrenia 1 is a protein that in humans is encoded by the DISC1 gene. In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth, mitochondrial transport, fission and/or fusion, and cell-to-cell adhesion. Several studies have shown that unregulated expression or altered protein structure of DISC1 may predispose individuals to the development of schizophrenia, clinical depression, bipolar disorder, and other psychiatric conditions. The cellular functions that are disrupted by permutations in DISC1, which lead to the development of these disorders, have yet to be clearly defined and are the subject of current ongoing research. Although, recent genetic studies of large schizophrenia cohorts have failed to implicate DISC1 as a risk gene at the gene level, the DISC1 interactome gene set was associated with schizophrenia, showing evidence from genome-wide association studies of the role of DISC1 and interacting partners in schizophrenia susceptibility.
Ninein is a protein that in humans is encoded by the NIN gene.
Kinesin-like protein KIF3A is a protein that in humans is encoded by the KIF3A gene.
Pericentrin (kendrin), also known as PCNT and pericentrin-B (PCNTB), is a protein which in humans is encoded by the PCNT gene on chromosome 21. This protein localizes to the centrosome and recruits proteins to the pericentriolar matrix (PCM) to ensure proper centrosome and mitotic spindle formation, and thus, uninterrupted cell cycle progression. This gene is implicated in many diseases and disorders, including congenital disorders such as microcephalic osteodysplastic primordial dwarfism type II (MOPDII) and Seckel syndrome.
Bardet–Biedl syndrome 4 is a protein that in humans is encoded by the BBS4 gene.
Katanin p80 WD40-containing subunit B1 is a protein that in humans is encoded by the KATNB1 gene.
Katanin p60 ATPase-containing subunit A1 is an enzyme that in humans is encoded by the KATNA1 gene.
Uncharacterized protein KIAA1377 is a protein that in humans is encoded by the KIAA1377 gene. Also known as Cep126, the protein has been shown to localize to the centrosome. Furthermore, it is found at pericentriolar satellites and the base of the primary cilium. Depleting Cep126 leads to dispersion of pericentriolar satellites, in turn disrupting microtubule organization at the mitotic spindle.
Centrosomal protein of 135 kDa is a protein that in humans is encoded by the CEP135 gene. It is part of the centrosome throughout the cell cycle, being distributed in the pericentriolar material. CEP135 is required for the centriolar localization of CEP250.
Neural precursor cell expressed, developmentally down-regulated 1, also known as Nedd1, is a human gene and encodes the protein NEDD1.
Tetratricopeptide repeat domain 8 (TTC8) also known as Bardet–Biedl syndrome 8 is a protein that in humans is encoded by the TTC8 gene.
Pericentriolar material is a highly structured, dense mass of protein which makes up the part of the animal centrosome that surrounds the two centrioles. The PCM contains proteins responsible for microtubule nucleation and anchoring including γ-tubulin, pericentrin and ninein.
Centrosomal protein of 192 kDa, also known as Cep192, is a protein that in humans is encoded by the CEP192 gene. It is the homolog of the C. elegans and D. melanogaster gene SPD-2.
Centrosomal protein of 164 kDa, also known as CEP164, is a protein that in humans is encoded by the CEP164 gene. Its function appears two be twofold: CEP164 is required for primary cilium formation. Furthermore, it is an important component in the response to DNA damage by UV light.
Centrosomal protein of 76 kDa, also known as CEP76, is a protein that in humans is encoded by the CEP76 gene.
Centrosomal protein of 78 kDa, also known as Cep78, is a protein that in humans is encoded by the CEP78 gene.
Centrosomal protein of 152 kDa, also known as Cep152, is a protein that in humans is encoded by the CEP152 gene. It is the ortholog of the Drosophila melanogaster gene asterless (asl) and both are required for centriole duplication.
Protein Hook homolog 2 (HK2) is a protein that in humans is encoded by the HOOK2 gene.