5.Cytoskeleton – Structure and Functions

Cytoskeleton – Structure and Functions, Intercellular Junctions

The Cytoskeleton

the cytoskeleton. This intricate network of protein filaments plays a crucial role in maintaining cell shape, facilitating movement, and supporting various cellular processes.

Microtubules:

Structure:
- Microtubules have an outer diameter of approximately 24 nm with a dense wall that is 5 nm thick. They also have a hollow lumen.
- The protein subunit of a microtubule is a heterodimer composed of α-tubulin and β-tubulin molecules.
- These tubulin heterodimers polymerize to form microtubules.
Function:
- Microtubules serve as rigid structures, contributing significantly to cell shape and stability.
- They participate in intracellular transport, allowing organelles and vesicles to move within the cell.
- During cell division (mitosis), microtubules form the mitotic spindle, ensuring proper chromosome segregation.
- Motor proteins associated with microtubules include:
  - Kinesins: These motor proteins move organelles away from the microtubule organizing centers (MTOCs) toward the plus end of microtubules.
  - Cytoplasmic Dyneins: They transport vesicles in the opposite direction, toward the minus end of microtubules.
Specialized Structures:
- Microtubules provide the basis for several complex cytoplasmic components, including:
  - Centrioles: These are part of the centrosome and play a crucial role in organizing microtubules during cell division.
  - Basal bodies: Found at the base of cilia and flagella, they control the assembly of the axoneme.
  - Cilia and flagella: These motile structures contain highly organized microtubule cores (9+2 pattern).

Microfilaments (Actin Filaments):

Structure:
- Microfilaments, also known as actin filaments, are the thinnest filaments of the cytoskeleton (approximately 5-7 nm in diameter).
- They consist of linear polymers of actin subunits.
Functions:
- Microfilaments are highly versatile:
  - They play a role in cytokinesis, the process of cell division.
  - Microfilaments are involved in changes in cell shape during processes like endocytosis, exocytosis, and cell locomotion.
  - They are closely associated with cytoplasmic organelles, vesicles, and granules, contributing to intracellular movement (cytoplasmic streaming).

Actin Binding Proteins:

Actin Motor Proteins:
- Myosin (II, I, V): These motor proteins move along microfilaments (actin filaments) and carry other molecules or vesicles. Myosin II is particularly important in muscle contraction.
Actin-Capping Proteins:
- Tropomyosin: Actin-capping proteins that bind to the free ends of actin filaments, regulating their stability and preventing disassembly.
Actin Filament Severing Proteins:
- Gelsolin: These proteins break microfilaments into shorter pieces, allowing for dynamic remodeling of the cytoskeleton.
Actin Bundling Proteins:
- Fimbrin, Villin, and Actinin: These proteins crosslink microfilaments, organizing them into bundles. They contribute to cell shape and stability.
Actin Branching Proteins:
- Formin: Formin proteins create branch points along a microfilament, promoting the formation of complex actin networks.

Intermediate Filaments:

Intermediate filaments have an average diameter of 10-12 nm, placing them between microtubules and microfilaments in size.
They are composed of various proteins and can be categorized into four major groups:
- Keratins (Cytokeratins): A diverse family of over 20 proteins found in epithelial cells and hard structures produced by epidermal cells. Keratins strengthen tissues and provide protection against abrasion and water loss.
- Vimentin: The most common intermediate filament protein in mesenchymal cells. Desmin (similar to vimentin) is found in almost all muscle cells, and Glial Fibrillary Acidic Protein (GFAP) is present in astrocytes (supporting cells of the CNS).
- Neurofilaments: These intermediate filaments are specific to neurons.
- Lamins: The nuclear lamina is a dense (~30 to 100 nm thick) fibrillar network inside the nucleus of most cells. It is composed of intermediate filaments and membrane-associated proteins. Besides providing mechanical support, the nuclear lamina regulates important cellular events such as DNA replication and cell division. Additionally, it participates in chromatin organization and anchors the nuclear pore complexes.

Cell Junctions:

Cell junctions play critical roles in cell adhesion, communication, and tissue integrity. Let’s explore some key types:

Intercellular Adhesion:

Tight Junctions (Occluding Junctions):
- These junctions seal adjacent cells together, preventing the flow of materials between them.
- Tight junctions are formed by occludin proteins.
Adhering Junctions (Anchoring Junctions):
- These sites of adhesion connect neighboring cells.
- They are made up of cadherin proteins.
Gap Junctions:
- Gap junctions allow direct communication between adjacent cells.
- They are formed by connexin proteins.
- These junctions are arranged in a specific order from the apical to the basal ends of cells:
  - Tight junctions 🡪 adhering junctions 🡪 desmosomes 🡪 gap junctions 🡪 hemidesmosomes.

Anchoring Junctions:

Desmosomes:
- Desmosomes serve as points of attachment between cells.
- They are anchored to intermediate filaments inside the cell.
- Desmosomes contribute to tissue strength and stability.
Hemidesmosomes:
- Hemidesmosomes bind epithelial cells to the basal lamina.
- While desmosomes contain cadherins, hemidesmosomes contain integrins (transmembrane proteins that act as receptor sites for extracellular macromolecules).
Adherent Junctions:
- Adherent junctions provide firm adhesion between neighboring cells.
- They connect to microfilaments (actin filaments) via catenin mediator proteins.

Intercellular Junctions: Intercellular junctions are specialized structures that connect adjacent cells within tissues. These junctions play essential roles in cell communication, tissue integrity, and function. Here are some key types of intercellular junctions:

Tight Junctions (Zonula Occludens):
- Tight junctions are found in epithelial tissues and serve as barriers between adjacent cells.
- They prevent the leakage of substances between cells by sealing the intercellular space.
- Tight junctions are formed by transmembrane proteins (e.g., claudins and occludins) that interact with each other.
- Examples include the tight junctions in the lining of the digestive tract, where they prevent the uncontrolled movement of nutrients and ions.
Adherens Junctions (Zonula Adherens):
- Adherens junctions are also present in epithelial tissues.
- They provide mechanical strength and stability to tissues.
- Adherens junctions are formed by cadherin proteins, which link adjacent cells via their extracellular domains.
- Inside the cell, cadherins connect to the actin cytoskeleton through proteins like α-catenin and β-catenin.
Desmosomes (Macula Adherens):
- Desmosomes are strong adhesive junctions found in tissues subjected to mechanical stress (e.g., skin, cardiac muscle).
- They consist of desmogleins and desmocollins (cadherin-like proteins) that bind adjacent cells.
- Intermediate filaments (keratin) anchor desmosomes to the cytoplasm, providing resilience against stretching and shearing forces.
Gap Junctions (Nexus):
- Gap junctions allow direct communication between adjacent cells.
- They form channels (connexons) that permit the exchange of ions, small molecules, and signaling molecules.
- Connexons are composed of connexin proteins.
- Gap junctions are crucial for coordinated activities in tissues like cardiac muscle and smooth muscle.
Hemidesmosomes:
- Hemidesmosomes anchor epithelial cells to the underlying basement membrane.
- They resemble half of a desmosome and connect integrins (transmembrane proteins) to intermediate filaments (e.g., keratin).
- Hemidesmosomes contribute to tissue stability and integrity.

These junctions collectively contribute to the proper functioning of multicellular organisms.