Cytoskeleton

The ability of eukaryotic cells to adopt a variety of shapes, organize many compartments in the interior, interact mechanically with the environment and carry out coordinated movement depends on cytoskeleton. The cytoskeleton is a network of fibers forming the “infrastructure” of eukaryotic cells, prokaryotic cells, and archaeans. In eukaryotic cells, these fibers consist of a complex mesh of protein filaments and motor proteins that aid in cell movement and stabilize the cell.
Cytoskeleton Function The cytoskeleton extends throughout the cell’s cytoplasm and directs a number of important functions.

• It helps the cell maintain its shape and gives support to the cell.
• A variety of cellular organelles are held in place by the cytoskeleton.
• It assists in the formation of vacuoles.
• The cytoskeleton is a highly dynamic structure and is able to disassemble and reassemble its parts in order to enable internal and overall cell mobility. Types of intracellular movement supported by the cytoskeleton include transportation of vesicles into and out of a cell, chromosome manipulation during mitosis and meiosis, and organelle migration.
• The cytoskeleton makes cell migration possible as cell motility is needed for tissue construction and repair, cytokinesis (the division of the cytoplasm) in the formation of daughter cells, and in immune cell responses to germs.
• The cytoskeleton assists in the transportation of communication signals between cells.
• It forms cellular appendage-like protrusions, such as cilia and flagella, in some cells.

Cytoskeleton Structure

The cytoskeleton is composed of at least three different types of protein fibers and motor proteins.

The Protein Fibers

The protein fibers: microfilaments, microtubules and intermediate filaments. These fibers are distinguished by their size with microtubules being the thickest and microfilaments being the thinnest.

Microfilaments

• Microfilaments are also known as actin filaments. They are thin, solid rods that are active in muscle contraction. Microfilaments are present in all eukaryotic cell. They are particularly prevalent in muscle cells. They also participate in organelle movement. Microfilaments are composed primarily of the contractile protein actin and measure up to 8 nm in diameter. Each filament is a twisted chain of identical globular actin (G actin). Actin filament has a structural polarity with a plus end and a minus end.

Ameoboid Movement

Actin polymerization causes protrusion. Protrusion means, the plasma membrane is pushed forward by the leading edge of the cell. This happens in Amoebae, macrophages, embryonic cells and metastatic cells.

Actin and cell junctions.
1. Adherens Junctions : Cadherin, Catenin, vinculin and actin.
2. Focal Adhesion : the sub-cellular structures that mediate the regulatory effects (i.e., signaling events) of a cell in response to ECM adhesion.

Actin Localizations

Different isoforms of actin are present in cell nucleus. Isoform means, those proteins are structurally related but functionally different from each other. Actin isoforms, despite of their high sequence similarity, have different biochemical properties such as polymerization and depolymerization kinetic. They also shows different localization and functions. The localizations are as followed.

1. Microvilli
2. Adhesion Belt
3. Cell Cortex
4. Filopodia
5. Lamellapodiam
6. Stress Fibres
7. Contractile Rings

Microtubules

Microtubules are the largest of the three components of the cytoskeleton present in all cell. They are hollow rods functioning primarily to help support and shape the cell and as “routes” along which organelles can move. Similar to microfilaments Microtubules are typically found in all eukaryotic cells. They vary in length and measure about 25 nm (nanometers) in diameter.
They are polymers of tubulin. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement. And non covalent bonding is used.

They grow from specialised organised centers. In animal cells they are centrosomes. The centrosome consist of a pair ofcentrioles surrounded by a matrix of proteins. The centrosome matrix includes 100s of ring shaped structures formed from γ-Tubulin and each γ-Tubulin ring complex serves as the starting point or nucleation site for the growth of one microtubule.

The αβ-tubulin dimers add to each γ-Tubulin ring complex in a specific orientation with the result that the minus end of each microtubule. Then it is embedded in the centrosome and growth occurs only at the plus end that extend into the cytoplasm.

La stathmin, or  oncoprotein 18” increased in tumor cells causing a turnover of microtubules

Microtubules maintain the structure of cell along with the microfilaments and intermediate filaments. They also form the internal structure of cilia and flagella. Intracellular transport is mainly occurred by these. And also the movement of secretory vesicles, organelles, and intracellular macromolecular assemblies (dynein and kinesin).
They are also involved in cell division (by mitosis and meiosis) and are the major constituents of mitotic spindles, which are used to pull eukaryotic chromosomes apart.

Microtubules are nucleated and organized by microtubule organizing centers (MTOCs), such as 

1. the centrosome found in the center of many animal cells.
2. the basal bodies found in cilia and flagella,
3. the spindle pole bodies found in most fungi.

The centrosome

The centrosome is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progression.

Centrosomes are formed by two centrioles. And thoes centrioles are arranged at perpendicular to each other. It is made of a cylindrical array of short microtubules (9 triplets). Yet centrioles have no role in the nucleation of the microtubules from the centrosome (The γ-Tubulin ring complex is sufficient). And it is surrounded by an amorphous mass of protein termed the pericentriolar material (PCM). Amorphorus means, it is a glassy solid and non crystalline. In general, each centriole of the centrosome is based on a nine triplet microtubule assembled in a cartwheel structure, and contains centrin, cenexin and tektin.

Following are the important functions of the centrosomes

• Assist in cell division during mitosis.
• They direct the movement of microtubules and cytoskeletal structures, thereby, facilitating changes in the shapes of the membranes of the animal cell.
• They play a role in mitosis in organizing the microtubules ensuring that the centrosomes are distributed to each daughter cell.
• Somehow act as the organizing centers for the microtubules in Cilia and Flagella where they are called basal bodies.
• They also stimulate the changes in the shape of the cell membrane by phagocytosis.
• They maintain the chromosome number during cell division.
• Centrosomes are associated with the nuclear membrane during the prophase stage of the cell cycle. In mitosis the nuclear membrane breaks down and the centrosome nucleated microtubules can interact with the chromosomes to build the mitotic spindle.

The Basal Bodies

A basal body is also known as basal granule, kinetosome and blepharoplast. It is formed from a centriole and several additional protein structures, and is, essentially, a modified centriole. The basal body serves as a nucleation site for the growth of the axoneme microtubules. Centrioles, from which basal bodies are derived, act as anchoring sites for proteins that in turn anchor microtubules, and are known as the microtubule organizing center (MTOC). These microtubules provide structure and facilitate movement of vesicles and organelles within many eukaryotic cells.

Mitotic Spindle

This is also known as spindle apparatus. And allows correct separation of the chromosome. This is formed during the cell division in order to seperate the sister chromatids between daughter cells. It has two different processes depending on the cell division type.

1. Mitotic Spindle : the mitotic spindle during mitosis, a process that produces genetically identical daughter cells.
2. Meiotic Spindle : the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell

Dynamic Stability of Microtubules

It allows microtubules to undergo rapid remoelling and is crucial for their function. In a normal cell, the centrosome is continually shooting out new microtubules in different directions in an exploratory fashion, many of which them react.

A microtubule growing out from the centrosome can however be prevented from dissassembling if its plus end is stabilized by attachment to another molecule or cell structure so as to prevent its depolymerization.

If stabilized by attachment to a structure in a more distant region of the cell, the microtubule will establish a relatively stable link between that structure and the centrosome.

The dynamic instability of microtubule is driven by GTP hydrolysis. Tubulin binds GTP, that can be hydrolized to GDP.

Intermediate filaments

Intermediate filaments have the great tensile strength. Intermediate filaments can be abundant in many cells and provide support for microfilaments and microtubules by holding them in place. These filaments form keratins found in epithelial cells and neurofilaments in neurons. They measure 10 nm in diameter.

Main Functions

• To enable the cell to withstand the mechanical stress that occur when cells are stretched. It is called “Intermediate” because, in the smooth muscle cells, they can be found between actin filaments and the thicker myosin filaments.
• Intermediate filaments are the toughest and the most durable of the cytoskeletal filaments. When cells are treated with concentrated salt solution and ionic detergents, the intermediate filaments survive, while most of the rest of the cytoskeleton is destroyed.
• Intermediate filaments are found in most of the animal cytoplasm. They typically form a network through out the cytoplasm, surrounding the nucleus and extending out to the cell periphery. There they are often anchored to the plasma membrane at cell-cell junctions. Desmosome and hemi desmosome where the plasma membrane is connected to that of another cell. 
• Also intermediate filament within the nucleus where they form nuclear lamina which underlies and strengthens the nuclear envelope.

Structure

• An intermediate filament is like a rope which many long strand are twisted together to provide tensile strength.
• Intermediate filament proteins are fibrous subunits each containing a central elongated rod domain with distinct unstructured domains at either end consists of an extended α-helical region that enables pairs of intermediate filament proteins to form stable dimers by wrapping around each other in a coiled coil configuration.
• Then staggered side by side arrangement of two dimers form tetromers.
• Tetromer is a basic unit for assembly of filaments. Tetromers can pack together into a helical array containing 8 tetromer strands which in turn assemble into the final rope-like intermediate filament.

Intermediate filaments can be grouped into 4 classes

1. Keratin filaments in epithelial cells
2. Vimentin and vimentin related filaments in connective tissue cells, muscle cells and glial cells
3. Neurofilaments in nerve cells
4. Nuclear lamina which strengthen the nuclear envelope

The Motor Proteins

A number of motor proteins are found in the cytoskeleton. As their name suggests, these proteins actively move cytoskeleton fibers. As a result, molecules and organelles are transported around the cell. Motor proteins are powered by ATP, which is generated through cellular respiration. They are dimers that have 2 globulat ATP biding heads and single tail. The head interacts with the microtubules. The tail generally binds to some cell component such as a vessicle or an organell. There are three types of motor proteins involved in cell movement.

• Kinesins move along microtubules carrying cellular components along the way. Generally moves toward the plus end of the microtubule. They are typically used to pull organelles toward the cell membrane.
• Dyneins are similar to kinesins and are used to pull cellular components inward toward the nucleus. Generally moves toward the minus end of the microtubule. Dyneins also work to slide microtubules relative to one another as observed in the movement of cilia and flagella.
• Myosins interact with actin in order to perform muscle contractions. They are also involved in cytokinesis, endocytosis (endo–cyt–osis), and exocytosis (exo-cyt-osis).

Cytoplasmic Streaming The cytoskeleton helps to make cytoplasmic streaming possible. Also known as cyclosis, this process involves the movement of the cytoplasm to circulate nutrients, organelles, and other substances within a cell. Cyclosis also aids in endocytosis and exocytosis, or the transport of substance into and out of a cell.
As cytoskeletal microfilaments contract, they help to direct the flow of cytoplasmic particles. When microfilaments attached to organelles contract, the organelles are pulled along and the cytoplasm flows in the same direction.
Cytoplasmic streaming occurs in both prokaryotic and eukaryotic cells. In protists, like amoebae, this process produces extensions of the cytoplasm known as pseudopodia. These structures are used for capturing food and for locomotion.

More Cell Structures The following organelles and structures can also be found in eukaryotic cells:

• Centrioles: These specialized groupings of microtubules help to organize the assembly of spindle fibers during mitosis and meiosis.
• Chromosomes: Cellular DNA is wrapped in thread-like structures called chromosomes.
• Cell Membrane: This semi-permeable membrane protects the integrity of the cell.
• Golgi Complex: This organelle manufactures, stores, and ships certain cellular products.
• Lysosomes: Lysosomes are sacs of enzymes that digest cellular macromolecules.
• Mitochondria: These organelles provide energy for the cell.
• Nucleus: Cell growth and reproduction are controlled by the cell nucleus.
• Peroxisomes: These organelles help to detoxify alcohol, form bile acid, and use oxygen to break down fats.
• Ribosomes: Ribosomes are RNA and protein complexes that are responsible for protein production via translation.