Introduction:
Cytoskeleton (CSK) is a complex, three-dimensional, dynamic network of interlinking protein filaments found in the cytoplasm of all cells which can be defined simply as “structural frame/ support of cells” (Cyto = Cell + Skeleton = structural support/ frame).
It is a complex network of protein filaments or fibres along with motor proteins that are held together by weak non-covalent bond, present in the cytoplasm of cells, including bacteria and archaea
The cytoskeleton organizes other constituents of the cell, maintains shape of the cell, and is responsible for the locomotion of the cell as well as the movement of the various organelles within it. The cell maintains endocytosis and phagocytosis while also stabilising cell attachment.
The cytoskeleton is a necessary structural framework for:
- Cell division: During cell division, the cytoskeleton regulates the movement of the chromosomes to the daughter nucleus.
- Cell movement: It promote the mobility of the cells.
- Cell shape: The shape of the cell is also determined by the cytoskeleton.
- Organelle movement: It can facilitate the movement of the organelles within the cell.
Components:
Major types of protein filaments that make up the cytoskeleton are:
Microfilaments (Actin Filaments)
Microfilaments, also known as actin filaments, occur in the cytoplasm of eukaryotic cells. These are the thinnest filaments in the cytoskeleton, measuring approximately 7 nm in diameter and made up of two actin strands. They are necessary for cell division, motility, and shape retention. Microfilaments also help muscles contract and create cell extensions such as microvilli and filopodia.
They are primarily composed of actin polymer, although they are modified and interact with varieties of other proteins in the cell. Actin is a family of globular multi-functional proteins that can be found as a free monomer called G-actin (globular) or as part of a linear polymer microfilament called F-actin. It is present in all eukaryotic cells. G-actin monomers unite to create a polymer, which then assembles into two chains that intertwine to generate F-actin chains.
Basically, actin act as tracks for the movement of myosin molecules that affix to the microfilament and “walk” along them.
Microfilament functions include
- Cytokinesis
- Amoeboid movement
- Cell motility
- Changes in cell shape
- Endocytosis and exocytosis
- Cell contractility
- Mechanical stability
Fig: Several components of cytoskeleton
Intermediate Filaments
These filaments are thicker than microfilaments but thinner than microtubules, with an average diameter of 8 to 10 nm. They are made up of various types of proteins, including keratins, vimentins, and neurofilaments, depending on the cell type.
They, like actin filaments, play a role in maintaining cell shape and anchoring the nucleus and other organelles in place through tension. They are unable to grow and deconstruct as quickly as actin filaments. Intermediate filaments are more persistent and have a structural role in the cell, providing mechanical strength and anchoring organelles in place.
Microtubules
These are the largest filaments of the cytoskeleton, composed of subunit of protein called tubulin.
Microtubules act as intracellular transport pathways, allowing organelles, vesicles, and other cellular components to move about. They are also required for cell division, as they form the mitotic spindle during mitosis and meiosis.
Fig: Structural component of microtubules
Microtubules are hollow cylinders about 22-25nm in diameter (lumen diameter of approximately 15 nm), most commonly comprising 13 protofilaments that, in turn, are polymers of alpha and beta tubulin.
Tubulin exits in three form including alpha tubulin, beta tubulin and gamma tubulin. The alpha and beta tubulin are arranged in a dimer fashion to form protofilaments. 13-15 protofilament come together to form and hollow cylinder, straw-shaped filaments that eventually form the microtubule that posses two distinct ends, called the plus (+) end showing β-subunits and minus (-) end showing α-subunits. Furthermore, the inner space of the hollow cylinder of microtubules is known as lumen.
The plus end also known as the “growing” end is characterized by the faster addition of tubulin subunits which faces outward toward the cell periphery. In contrast, the minus end of a microtubule is characterized by slower addition or loss of tubulin subunits.
α- and β-tubulins bind to GTP for polymerization or depolymerization. GTP coupled to β-tubulin hydrolyses to GDP during polymerization. The alteration reduces tubulin binding affinity, resulting in depolymerization and microtubule dynamics. Microtubules undergo a process called as treadmilling. In this mechanism, tubulin molecules attached to GDP are constantly removed from the negative end and replaced by tubulin with GTP at the positive end of the same microtubule.
Intracellular transport, mitotic spindle, synthesis of the cell wall in plants are some of the major functions of microtubules.
Diseases and cytoskeleton:
- Cytoskeletal protein abnormalities are the root cause of many disease phenotypes. It is hardly surprising that changes to such an important cellular structure result in disease disorders. Many diseases have now been linked to anomalies in cytoskeletal and nucleoskeletal proteins, including numerous cardiovascular disease syndromes, neurodegeneration, cancer (invasion), liver cirrhosis, pulmonary fibrosis, and blistering skin disease.
- Immotile cilia syndrome is caused by ciliary cytoskeleton anomalies, which impair ciliary function and lead to further symptoms.
- Cytoskeletal component dysfunction can have an impact on vesicular biogenesis, vesicle/organelle trafficking, and synaptic signaling.
- Mutations in erythroid membrane skeleton proteins induce hereditary haemolytic anaemia and have additional consequences.
- Keratin mutations are associated with genetic skin fragility illnesses, as well as liver and inflammatory bowel diseases.