Cytoskeleton: Structure, Function & Diseases

The cytoskeleton consists of a dynamically variable network of three different protein filaments in the cytoplasm of cells. They provide structure, strength, and intrinsic mobility (motility) to the cell and to organizational intracellular entities such as organelles and vesicles. In some cases, the filaments project out of the cell in the form of cilia or flagella to aid in cell motility or the directional transport of foreign bodies.

What is the cytoskeleton?

The cytoskeleton of human cells consists of three distinct classes of protein filaments. Microfilaments (actin filaments), 7 to 8 nanometers in diameter and composed mainly of actin proteins, serve to stabilize the external cell shape and motility of the cell as an overall unit as well as intracellular structures. In muscle cells, actin filaments enable coordinated contraction of muscles. Intermediate filaments, which are about 10 nanometers thick, also serve to provide mechanical strength and structure to the cell. They are not involved in cell motility. Intermediate filaments are composed of various proteins and dimers of the proteins that combine to form rope-like coiled bundles (tonofibrils) and are extremely tear-resistant structures. Intermediate filaments can be divided among themselves into at least 6 different types with different tasks. The third class of filaments consists of tiny tubes, microtubules with an outer diameter of 25 nanometers. They are composed of polymers of tubulin dimers and are mainly responsible for all types of intracellular motility and for the motility of the cells themselves. To support the intrinsic motility of cells, microtubules can form cell processes in the form of cilia or flagella that extend out of the cell. The meshwork of microtubules is usually organized from the centromere and is subject to extremely dynamic changes.

Anatomy and structure

The substance groups microfilaments, intermediate filaments (IF), and microtubules (MT), all three of which are assigned to the cytoskeleton, are almost omnipresent within the cytoplasm and also within the nucleus. The basic building blocks of human microfilaments or actin filaments consist of 6 isoform actin proteins, each differing by only a few amino acids. The monomeric actin protein (G-actin) binds the nucleotide ATP and forms long molecular chains of actin monomers, each cleaving off a phosphate group, two of which combine to form helical actin filaments. The actin filaments in smooth and striated muscle, in cardiac muscle and the non-muscular actin filaments each differ slightly from one another. Buildup and breakdown of actin filaments are subject to very dynamic processes and adapt to requirements. Intermediate filaments are composed of different structural proteins and achieve high tensile strength at a cross-section of about 8 to 11 nanometers. Intermediate filaments are divided into five classes: acidic keratins, basic keratins, desmin-type, neurofilaments and lamin-type. While the keratins are found in epithelial cells, the desmin-type filaments are found in smooth and striated muscle cells and in cardiac muscle cells. Neurofilaments, present in virtually all neurons, are composed of proteins such as internexin, nestin, NF-L, NF-M, and others. Lamin-type intermediate filaments are found in all nuclei within the nuclear membrane in the karyoplasm.

Function and roles

The function and tasks of the cytoskeleton are by no means limited to structural shape and stability of cells. Microfilaments, located mainly in reticular structures immediately adjacent to the plasma membrane, stabilize the external shape of cells. However, they also form membrane protrusions such as pseudopodia. Motor proteins, of which the microfilaments in the muscle cells are composed, provide the necessary contractions of the muscles. The greatest importance for the mechanical strength of the cells is attached to the very tensile intermediate filaments. In addition, they perform a number of other functions. Keratin filaments of the epithelial cells are indirectly mechanically connected to each other via desmosomes, giving the skin tissue a two-dimensional, matrix-like, strength.Via intermediate filament-associated proteins (IFAPs), the IFs are connected with the other groups of substances of the cytoskeleton, provide for a certain exchange of information and for the mechanical strength of the corresponding tissue. This results in ordered structures within the cytoskeleton. Enzymes such as kinases and phosphatases ensure rapid assembly, remodeling and disassembly of the networks. Different types of neurofilaments stabilize nervous tissue. Lamins control the dissolution of the cell membrane during cell division and its subsequent reconstruction. Microtubules are responsible for tasks such as controlling the transport of organelles and vesicles within the cell and organizing chromosomes during mitosis. In cells in which microtubules form microvilli, cilia, flagella, or flagella, MTs also provide motility for the entire cell or handle the removal of mucus or foreign bodies, such as in the trachea and external auditory canal.

Diseases

Disorders in the metabolism of the cytoskeleton can result either from genetic defects or from toxins introduced from the outside. One of the most common inherited diseases associated with a disorder in the synthesis of a membrane protein for muscles is Duchenne-type muscular dystrophy. A genetic defect results in the failure to produce dystrophin, a structural protein required in muscle fibers of striated skeletal muscle. The disease occurs in early childhood with a progressive course. Mutated keratins can also lead to serious effects. Ichthyosis, the so-called fish scale disease, results in hyperkeratosis, an imbalance between production and exfoliation of skin scales, because of one or more genetic defects on chromosome 12. Ichthyosis is the most common, hereditary, disease of the skin and requires intensive therapy, which, however, can only alleviate symptoms. Other genetic defects, which lead to a disturbance of the metabolism of the neurofilaments, cause, for example, amyotrophic lateral sclerosis (ALS). Some known mycotoxins (fungal toxins) such as those from molds and fly agarics disrupt actin filament metabolism. Colchicines, the toxin of the autumn crocus, and taxol, which is extracted from yew trees, are used specifically for tumor therapy. They interfere with microtubule metabolism.