Centrosome
The Microtubule Organizing Center (MTOC) is a structure from which microtubules emerge. The concept of MTOCs was established due to advances in microscopy techniques, enabling researchers to visualize structures that assemble and organize microtubules. The most well-studied MTOCs are the centrosome in animal cells and the spindle pole body in yeast, however there are also other sites within cells where organization of microtubules occur
(Lüders J et al, 2007.). In mammalian cells, the most prominent and well-known MTOC is the centrosome, which has been widely studied ever since Theodor Bovery first described it in 1888
(Bovery, T, 1900). Although the centrosome is a small organelle, its impact on cellular function is of great importance. Located adjacent to the nucleus, the major role of the centrosome is to regulate the intracellular organization of the microtubules, which is important during cell division when the mitotic spindle is formed. The centrosome is the key responsible organelle for the correct orientation of the poles of the mitotic spindle, facilitating the segregation of the chromosomes, and the subsequent distribution to the daughter cells
(Nigg EA et al, 2011). Of all proteins detected in the Cell Atlas,
466 proteins (2%) have been experimentally shown to localize to the MTOC.
In images where it has been possible to distinguish the centrioles, proteins have been annotated with the location Centrosome.
In images where the centrioles have not been detected, but the protein localizes to the center of the microtubules, proteins have been
annotated with the location MTOC (Figure 1-2). Functional enrichment analysis of the MTOC proteome shows highly enriched terms for
biological processes related to organization of the microtubules and cell cycle progression (Figure 3).
The structure of the centrosome
Structures Microtubule organizing center: 132
Centrosome: 336
The centrosome is a small non-membranous MTOC organelle occupying about 1-2 μm3 of the cytoplasmic volume
(Doxsey S, 2001). It is composed of two barrel shaped centrioles, each having nine proximal triplets organized into a symmetric structure, which maintain both the stability and functional activity of the centrosome. The centrioles are organized in a matrix together with proteins, commonly referred to as the pericentriolar material (PCM). Among the proteins of this complex, there are many important cell cycle regulators and other signaling molecules essential for the function of the centrosome. Pericentrin (Figure 1), aurora kinases, ninein and centriolin are some examples
(Doxsey S, 2001). Also, several of the proteins that are localized to MTOC belong to these PCM proteins. One of the most well studied constituents of the PCM is the highly conserved γ-tubulin protein complex, which is organized into an open ring structure with around 25 nm in diameter, responsible for the nucleation of the microtubules. As a key regulator of mitosis, the MTOC displays a highly dynamic structure that undergoes dramatic organizational changes throughout the cell cycle
(Bornens M, 2002; Conduit PT et al, 2015).
Table 1. Selection of proteins suitable as markers for the MTOC.
Gene |
Description |
Substructure |
|
MKKS
|
McKusick-Kaufman syndrome |
Centrosome |
|
ODF2
|
Outer dense fiber of sperm tails 2 |
Centrosome |
|
CEP97
|
Centrosomal protein 97kDa |
Cytosol
Microtubule organizing center |
|
KIF5B
|
Kinesin family member 5B |
Cytosol
Microtubule organizing center |
|
PIBF1
|
Progesterone immunomodulatory binding factor 1 |
Microtubule organizing center
Nucleoplasm |
The function of the centrosome
The major functional role of MTOCs is to manage the organization of the microtubules in the cell; they thereby possess an important influence over the cellular shape, polarity, proliferation and mobility. In eukaryotic cells, one of the major MTOCs is the well-studied centrosome that is associated with spindle formation during cell division. During S-phase the centrioles are first duplicated into daughter centrioles that start to move apart as the cell enters mitosis (G2-M phases) and the amount of surrounding PCM increases. Proteins in the PCM contribute to the assembly and orientation of the mitotic spindle by organizing into a scaffold structure around the mother centrioles, where they facilitate spindle formation through different functions. Increasing evidence suggest a more versatile function of the centrosome, especially pointing to its ability to coordinate a myriad of cellular functions by serving as a compact hub where cytoplasmic proteins can interact at higher concentrations
(Doxsey S, 2001; Rieder CL et al, 2001). As a key regulator of the cell cycle, abnormalities in number, size and morphology of the centrosome is commonly observed in cells undergoing tumorigenesis. Centrosomal abnormalities are also observed in several other diseases. Dysfunction in the ubiquitin-proteasome degradation that has implications in several neurodegenerative disorders is one example
(Badano JL et al, 2005). Gene Ontology (GO)-based analysis of the corresponding genes in the MTOC proteome shows functions that are well in-line with existing literature on MTOC and centrosome function. The most highly enriched terms for the GO domain Biological Process are related to the organization of the microtubules, cell division and cilium morphogenesis (Figure 3a). Enrichment analysis of the GO domain Molecular Function, also generates expected results showing dynein- and tubulin binding together with motor activity as the most enriched significant terms (Figure 3b). A list of highly expressed MTOC and centrosome proteins are summarized in Table 2.
Table 2. Highly expressed MTOC and centrosome marker proteins, in different cell lines.
Gene |
Description |
Average TPM |
|
RAB11A
|
RAB11A, member RAS oncogene family |
265 |
|
KIAA0101
|
KIAA0101 |
201 |
|
DCTN2
|
Dynactin 2 (p50) |
106 |
|
MAP1LC3B
|
Microtubule-associated protein 1 light chain 3 beta |
54 |
|
ODF2
|
Outer dense fiber of sperm tails 2 |
52 |
|
PAFAH1B1
|
Platelet-activating factor acetylhydrolase 1b, regulatory subunit 1 (45kDa) |
50 |
|
MKKS
|
McKusick-Kaufman syndrome |
41 |
|
RMDN1
|
Regulator of microtubule dynamics 1 |
40 |
|
CETN3
|
Centrin, EF-hand protein, 3 |
31 |
|
CEP250
|
Centrosomal protein 250kDa |
28 |
Centrosome and the MTOC proteins with multiple locations
Approximately 76% (n=353) of the centrosome and MTOC proteins detected in the cell atlas also localize to other cellular compartments (Figure 4). The network plot shows that the most common locations shared with Centrosome and MTOC are the cytoplasm, nucleus and vesicles.
Expression levels of centrosome proteins in tissue
Transcriptome analysis (Figure 5) shows that centrosome and MTOC proteins are less likely to be expressed at equal levels in all tissue types, compared to all genes with protein data in the Cell Atlas.
Relevant links and publications
Badano JL et al, 2005. The centrosome in human genetic disease. Nat Rev Genet.
PubMed: 15738963 DOI: 10.1038/nrg1557 Bornens M. 2002. Centrosome composition and microtubule anchoring mechanisms. Curr Opin Cell Biol.
PubMed: 11792541 Bovery T. 1900. Zellen-Studien. Verlag von Gustav Fischer. Conduit PT et al, 2015. Centrosome function and assembly in animal cells. Nat Rev Mol Cell Biol.
PubMed: 26373263 DOI: 10.1038/nrm4062 Doxsey S. 2001. Re-evaluating centrosome function. Nat Rev Mol Cell Biol.
PubMed: 11533726 DOI: 10.1038/35089575 Lüders J et al, 2007. Microtubule-organizing centres: a re-evaluation. Nat Rev Mol Cell Biol.
PubMed: 17245416 DOI: 10.1038/nrm2100 Nigg EA et al, 2011. The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries. Nat Cell Biol.
PubMed: 21968988 DOI: 10.1038/ncb2345 Rieder CL et al, 2001. The centrosome in vertebrates: more than a microtubule-organizing center. Trends Cell Biol.
PubMed: 11567874 |
