PCM1
Encyclopedia
Pericentriolar material 1, also known as PCM1, is a protein
which in humans is encoded by the PCM1 gene
.
-dependent association with the centrosome
complex and microtubule
s. 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. 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.
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
).
. In humans it is expressed above the median level of central nervous system (CNS) expression in most parts of the brain.
. 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.
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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the PCM1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
The PCM1 protein was originally identified by virtue of its distinct cell cycleCell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
-dependent association with the centrosome
Centrosome
In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden in 1883...
complex and microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
s. 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
Immunolabeling
Immunolabeling is a means of localizing particular antigens within tissue. Immunolabeling is a methodological process where: 1) antibodies are used to identify antigens within an organism and 2) a tag is added to a secondary antibody which binds to the primary antibody...
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
Centrin
Centrins, also known as caltractins, are a family of calcium-binding phosphoproteins found in the centrosome of eukaryotes. Centrins are present in the centrioles and pericentriolar lattice. Human centrin genes are CETN1, CETN2 and CETN3.-Function:...
, pericentrin
PCNT
Pericentrin , also known as PCNT, is a protein which in humans is encoded by the PCNT gene.- Function :The protein encoded by this gene binds to calmodulin and is expressed in the centrosome. It is an integral component of the pericentriolar material...
and ninein
NIN (gene)
Ninein is a protein that in humans is encoded by the NIN gene. Ninein, together with its paralog Ninein-like protein is one of the proteins important for centrosomal function. This protein is important for positioning and anchoring the microtubules minus-ends in epithelial cells...
was also dramatically reduced after PCM1 depletion using siRNA, overexpression of PCM1 deletion mutants and PCM1 antibody microinjection. 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
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 coilCoiled coil
A coiled coil is a structural motif in proteins, in which 2-7 alpha-helices are coiled together like the strands of a rope . Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression e.g. transcription factors...
regions between areas of low complexity as well as an adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
(ATP
ATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...
) / GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
domain, a nuclear localization
Nuclear localization signal
A nuclear localization signal or sequence is an amino acid sequence which 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different...
domain and a eukaryotic molybdopterin domain. The eukaryotic molybdopterin binding domain is currently found in only five other human genes, xanthine dehydrogenase
Xanthine dehydrogenase
Xanthine dehydrogenase, also known as XDH, is a protein that, in humans, is encoded by the XDH gene.-Function:Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The enzyme is a homodimer...
, sulfite oxidase
Sulfite oxidase
Sulfite oxidase is an enzyme in the mitochondria of all eukaryotes. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ATP in oxidative phosphorylation...
(mitochondrial precursor), aldehyde oxidase
Aldehyde oxidase
Aldehyde oxidase is an enzyme which generates carboxylic acids from aldehydes. It catalyzes the conversion of an aldehyde in the presence of oxygen and water to an acid and hydrogen peroxide.* an aldehyde + H2O + O2 a carboxylate + H2O2 + H+...
, erythropoietin receptor
Erythropoietin receptor
The erythropoietin receptor is a protein that in humans is encoded by the EPOR gene. EpoR is a 59 kDa peptide and is a member of the cytokine receptor family. EpoR pre-exists as dimers...
precursor and the ATPbinding cassette, sub-family A, member 2 (ABCA2
ABCA2
ATP-binding cassette sub-family A member 2 is a protein that in humans is encoded by the ABCA2 gene.- External links :...
).
Tissue distribution
PCM1 mRNA expression in the mouse brain has been found to be highest in the hippocampusHippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
. In humans it is expressed above the median level of central nervous system (CNS) expression in most parts of the brain.
Clinical significance
Mutations in the PCM1 gene have been shown to cause genetic susceptibility to schizophreniaSchizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. 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.
PCM1 forms a complex at the centrosome
Centrosome
In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden in 1883...
with disrupted-in-schizophrenia 1 (DISC1
DISC1
Disrupted in schizophrenia 1 is a protein that is encoded by the DISC1 gene in humans. 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,...
) and Bardet-Biedl syndrome 4 protein (BBS4
BBS4
Bardet-Biedl syndrome 4 protein is a protein that in humans is encoded by the BBS4 gene.This gene encodes a protein which contains tetratricopeptide repeats , similar to O-linked N-acetylglucosamine transferase. Mutations in this gene have been observed in patients with Bardet-Biedl syndrome type 4...
), which provides a link between aberrant PCM1 and the abnormal cortical development associated with the pathology of schizophrenia.