Centrosomes are structures found within the cytoplasm of animal cells, usually positioned near the nucleus. They act as the primary microtubule-organizing center (MTOC) for the cell, serving as a central hub for the assembly and organization of microtubules. These structures are composed of two cylindrical centrioles arranged perpendicularly to each other, surrounded by a dense network of proteins called the pericentriolar material (PCM). The PCM is rich in proteins like gamma-tubulin, pericentrin, and ninein, which are responsible for initiating and anchoring microtubules. Centrosomes are important for various cellular processes, providing structural support and influencing cell function.
Orchestrating Cell Division
Centrosomes play a central role in cell division, both in mitosis and meiosis, by organizing the mitotic spindle. Before a cell divides, during the S phase of the cell cycle, the centrosome duplicates, ensuring each new daughter cell receives one. These duplicated centrosomes then migrate to opposite poles of the cell as division begins.
From these poles, microtubules assemble into spindle fibers, forming the mitotic spindle. These spindle fibers attach to the chromosomes at structures called kinetochores and accurately pull replicated chromosomes apart. This separation ensures each daughter cell receives a complete and identical set of chromosomes, maintaining genetic stability.
Directing Cellular Movement
Centrosomes also direct cellular movement, particularly as basal bodies. In many cell types, one centriole (the “mother” centriole) can transform into a basal body. Basal bodies serve as anchoring points for cilia and flagella, hair-like projections extending from the cell surface.
Cilia and flagella facilitate cellular movement. Flagella, often longer and fewer, enable the propulsion of cells like sperm. Cilia, shorter and more numerous, can move entire cells, such as Paramecium, or move substances across cell surfaces, as in the respiratory tract to clear mucus. This ability demonstrates the centrosome’s influence on cell motility and fluid transport.
Establishing Cell Organization
Centrosomes contribute to establishing and maintaining cell polarity, the asymmetrical organization of cellular components. In non-dividing cells, the centrosome positions near the cell’s center, close to the nucleus, with microtubules radiating outwards. This arrangement helps dictate cell shape and the internal positioning of organelles.
In specialized cells, such as epithelial cells or neurons, centrosome positioning is important for their distinct functions. In polarized epithelial cells, centrosomes are located on the apical (top) surface, contributing to their top-to-bottom organization and influencing microtubule arrangement along this axis. This ordered internal structure is important for directed cellular activities, including cell migration and the outgrowth of neuronal processes.
Centrosomes and Human Health
Dysfunction of centrosomes impacts human health, contributing to various diseases. Cancer is one area where centrosome abnormalities are often observed. These abnormalities can include an increased number of centrosomes (centrosome amplification) or structural defects. Such issues can lead to errors during cell division, resulting in aneuploidy—an unequal distribution of chromosomes to daughter cells. Aneuploidy is a hallmark of many cancer cells and can promote tumor development and progression by increasing genomic instability.
Centrosome dysfunction is also linked to a group of genetic disorders called ciliopathies. These conditions arise from defects in the formation or function of cilia, which are built upon centrosome-derived basal bodies. Ciliopathies can cause diverse symptoms affecting multiple organ systems, including kidney cysts, developmental brain defects like microcephaly, and respiratory problems due to impaired mucociliary clearance. Mutations in genes encoding centrosomal proteins, such as CEP290, are associated with Joubert syndrome, a ciliopathy affecting brain development.