UNIT 13 – Extracellular Matrix and Cell Junctions (Q&A) | MZO-001 MSCZOO | IGNOU
SAQ 1
a) All proteoglycans are with GAG side chains and sulphated, except which one?
Answer: Hyaluronic acid
b) Name the four main families of CAMs.
Answer: Integrins, Immunoglobulin superfamily, Cadherins and Selectins
c) Out of the following which is not a cell-cell junction?
i) tight junctions
ii) gap junctions
iii) desmosomes
iv) hemidesmosomes
Answer: iv) hemidesmosomes
d) What will happen if the Ca2+ is removed from the tight junction?
Answer: Ca²⁺ is necessary for tight-junction integrity, and if it is removed, undesirable diffusion of membrane components will take place.
SAQ 2
a) Connexons present in gap junctions comprise of how many membrane protein?
Answer: 6
b) Tight junctions are held together by a specific protein called ...................... .
Answer: Claudins
TERMINAL QUESTIONS
1. Write a brief note about the cell junction, their types and functions.
Cell junctions are specialized structures that act as links between adjacent cells, playing a key role in maintaining the structural and functional integrity of tissues in multicellular organisms. They facilitate direct communication between cells, ensuring coordinated cellular functions. By regulating processes like cell adhesion, signal transmission and permeability, cell junctions help in maintaining tissue architecture and allow cells to respond to changes in their environment. These junctions are critical for tissue homeostasis, development and various physiological functions.
Types of Cell Junctions and Their Functions:
Based on the function of how cells connect and interact with each other, cell junctions are classified into three types:
- Tight Junctions (Occluding Junctions) – which block movement
- Anchoring Junctions – which provide mechanical stability
- Gap Junctions (Communicating Junctions) – which allow exchange of signals or materials between cells
1. Tight Junctions (Occluding Junctions):
Tight junctions, also known as occluding junctions, are formed by transmembrane proteins like claudins and occludins, which seal the intercellular space between adjacent cells. These junctions create a barrier that prevents the leakage of extracellular fluids and ions between cells. They are particularly prominent in epithelial tissues, such as those lining the intestines, blood-brain barrier and kidneys. Tight junctions regulate the paracellular transport of ions and small molecules, ensuring that molecules pass through the cells rather than between them.
Function:
- Tight junctions act as a selective barrier, preventing the uncontrolled flow of substances between cells and maintaining the distinct internal and external environments of tissues. They are crucial in maintaining tissue polarity, where the apical and basolateral surfaces of the cells remain functionally distinct.
2. Anchoring Junctions:
Anchoring junctions are specialized cell structures that help in holding cells tightly in place within a tissue. They provide physical strength by connecting cells directly to neighbouring cells or between a cell and the extracellular matrix (ECM). These junctions are essential in tissues that experience continuous mechanical stress or pressure, such as the skin, heart muscle and uterus. They connect the internal cytoskeleton of a cell to specific proteins at the membrane, creating a stable support system. Anchoring junctions are not uniform; they are mainly divided into three types based on the structure they connect to: adherens junctions, desmosomes and hemidesmosomes. Each type has a different role but all work to give tissues mechanical support and stability.
a) Adherens Junctions (Zonula Adherens)
Adherens junctions connect the actin cytoskeleton of one cell to the actin cytoskeleton of another cell (cell-to-cell junctions) using cadherin proteins, which are calcium-dependent adhesion molecules. These junctions form continuous belts around the cells and are located just below tight junctions. They help maintain the shape of cells and support coordinated movements in epithelial sheets, such as during embryonic development.
Function:
- They maintain tissue shape, help in morphogenesis during development, and resist mechanical disruption by forming a continuous adhesion belt around the cells.
b) Desmosomes (Macula Adherens)
Desmosomes are also cell-to-cell junctions, but instead of actin filaments, they connect the intermediate filaments (like keratin) of two adjacent cells. The connection is made via desmoglein and desmocollin proteins, which are types of cadherins protein. These junctions act like spot welds between cells. Desmosomes are mainly found in tissues that experience strong mechanical forces like the epidermis and cardiac muscle.
Function:
- They provide strong, spot-like adhesions that help cells withstand shear stress and mechanical force without getting separated.
c) Hemidesmosomes
Unlike the previous two, hemidesmosomes are cell-to-extracellular matrix junctions. Hemidesmosomes are similar in appearance to desmosomes but perform a different role. Instead of linking two cells, they connect the basal side of epithelial cells to the basement membrane. They use integrin proteins to attach the cytoskeleton (especially intermediate filaments) to extracellular matrix proteins like laminin.
Function:
- They help stabilize epithelial layers by attaching them firmly to the basement membrane, ensuring that cells do not get detached under mechanical force.
3. Gap Junctions (Communicating Junctions):
Gap junctions are specialized connections that allow direct communication between adjacent cells. These junctions are formed by connexins, which are proteins that assemble into channels known as connexons. These channels permit the passage of ions, small molecules and electrical signals between cells, enabling coordinated cellular responses. Gap junctions are abundant in tissues such as cardiac muscle, smooth muscle and neurons, where cell-to-cell communication is essential for synchronizing functions like contraction or neurotransmission.
Function:
- Gap junctions facilitate intercellular communication by allowing the direct exchange of ions and molecules. They are vital for coordinating the activity of large groups of cells, such as in the heart, where they ensure the synchronized contraction of cardiac muscle cells. Gap junctions also play a role in the spread of electrical signals in nerve tissues.
2. Which type of cell junction is similar to plamosdesmata? Give a detailed account on gap junction.
The type of cell junction that is similar to plasmodesmata is the gap junction. Both allow the direct transfer of ions, small molecules and chemical signals between neighboring cells. Plasmodesmata are found in plant cells, while gap junctions are their functional counterparts in animal cells.
Gap Junction
Gap junctions are a type of communicating cell junction found in animal cells. These structures form direct channels between adjacent cells, allowing for the transfer of ions, metabolites and small signaling molecules. They play a crucial role in maintaining tissue homeostasis, cell communication and coordinated cellular responses. These junctions are especially important in tissues that require rapid and synchronized communication like cardiac muscle, smooth muscle and certain neural tissues.
Structure of Gap Junctions
Gap junctions are composed of transmembrane protein subunits known as connexins. Six connexin molecules come together to form a connexon (also called a hemichannel). One connexon from one cell aligns with another connexon from the neighboring cell to form a complete intercellular channel. This channel directly connects the cytoplasm of the two cells, allowing substances smaller than ~1 kDa (like ions, glucose, cyclic AMP, ATP) to pass freely.
There are over 20 different types of connexins in humans, and their composition can influence the permeability and regulation of gap junctions. For example, Connexin 43 is commonly found in heart tissue and its proper function is vital for electrical conduction in cardiac muscle.
Functions of Gap Junctions
Gap junctions are important for:
- Intercellular communication: They allow neighboring cells to exchange chemical signals, ensuring coordinated responses in tissues.
- Electrical coupling: In cardiac and smooth muscle cells, they enable the rapid spread of action potentials, allowing muscle cells to contract in unison.
- Metabolic cooperation: They help in the sharing of small metabolites between cells, which can be important for growth and survival, especially during stress.
- Development and differentiation: During embryogenesis, gap junctions help maintain communication among developing cells, guiding proper tissue and organ formation.
Regulation of Gap Junctions
Gap junction channels are not always open. Their permeability can be regulated by various factors such as intracellular calcium levels, pH and phosphorylation. For example, a high concentration of intracellular calcium (which may indicate cell damage) causes the gap junctions to close, preventing the spread of harmful substances to healthy neighboring cells.
Comparison with Plasmodesmata
Although gap junctions and plasmodesmata serve similar roles in cell-to-cell communication, their structures are different. Plasmodesmata are more complex and allow the transport of larger molecules like proteins and RNA, whereas gap junctions are limited to smaller molecules. Also, plasmodesmata are permanent structures, while gap junctions can be assembled or disassembled depending on the cell's needs.
3. What is the difference between desmosomes and hemidesmosomes?
Desmosomes and hemidesmosomes are two important types of anchoring junctions that help maintain the structural stability of tissues. These junctions are mainly found in epithelial tissues and other tissues that experience mechanical stress like heart muscles and skin. While both are involved in anchoring functions and connect to intermediate filaments inside the cell, they still differ based on several aspects such as:
1. Based on Definition and Location
Desmosomes are specialized intercellular junctions that form strong adhesion between two adjacent cells. They are mainly located in tissues that need to withstand stretching and pressure, such as cardiac muscles and stratified epithelium.
Hemidesmosomes, on the other hand, are junctions that connect the basal surface of epithelial cells to the basement membrane. They are especially found in the skin, where they attach the lower layer of epidermis to the dermis.
2. Based on Shape and Structure
Desmosomes appear as round, button-like or disc-shaped structures located at the lateral surfaces of cells where two cells are tightly joined.
In contrast, hemidesmosomes appear as half-disc or semi-circular structures located only at the basal surface of the epithelial cells, attaching them to the basement membrane.
3. Based on Visibility under electron microscope
Under an electron microscope, desmosomes appear as symmetrical dense plaques on both adjacent cell membranes, giving a mirror-like image.
Hemidesmosomes, however, appear asymmetrical and are seen only on one side, at the basal plasma membrane of the cell, where it attaches to the extracellular basement membrane.
4. Based on Type of Connection
Desmosomes form a cell-to-cell connection. They link the plasma membrane of one cell to the plasma membrane of another neighboring cell.
Hemidesmosomes form a cell-to-extracellular matrix connection. They link the epithelial cell to the basement membrane, not to another cell.
5. Based on Protein Composition
Desmosomes use cadherin family proteins, especially desmoglein and desmocollin, which extend from the cell membrane and form homophilic interactions with cadherins of the neighboring cell. Inside the cell, these proteins connect to plaque proteins such as plakoglobin, plakophilin and desmoplakin, which in turn anchor to keratin intermediate filaments.
Hemidesmosomes use integrin family proteins, mainly α6β4 integrins, which bind to laminin-332 in the basal lamina. Internally, integrins connect to proteins like plectin and BP230 (bullous pemphigoid antigen 1), which bind to keratin intermediate filaments.
6. Based on Interaction Type
Desmosomes use homophilic interactions between cadherin proteins, like desmoglein and desmocollin, that bind similar proteins on neighboring cells.
Hemidesmosomes use heterophilic interactions, where integrins on the basal cell surface bind to different extracellular proteins like laminin in the basement membrane.
7. Based on Function
Desmosomes provide mechanical strength and stability between adjacent cells. They act like spot welds or rivets and help resist shearing forces.
Hemidesmosomes provide anchorage to the basement membrane and help in cell-matrix adhesion, preventing the detachment of epithelial cells from the underlying connective tissue.
8. Based on Diseases Involved
Desmosomal defects can cause pemphigus vulgaris, an autoimmune disorder where antibodies target desmogleins, leading to loss of cell adhesion and blistering.
Hemidesmosomal defects can lead to bullous pemphigoid, where antibodies target proteins like BP230 or BP180, causing separation of the epidermis from the dermis.
4. What is the role of cadherin in cell-cell adhesions?
Cadherins are a large family of calcium-dependent transmembrane glycoproteins that play a key role in forming and maintaining cell-to-cell adhesions in animal tissues. These proteins are most active in epithelial, neural and cardiac tissues where strong cell-cell interactions are needed. The term "cadherin" comes from "calcium-dependent adhesion", meaning they require calcium ions (Ca²⁺) to function properly. Their adhesive function is mainly homophilic, where cadherin molecules on one cell bind to the same type of cadherin on the neighboring cell. Cadherins are primarily involved in forming adherens junctions and desmosomes, which are responsible for strong cell-cell adhesion in tissues under mechanical stress.
Cadherins are not only essential for sticking cells together but also for helping maintain the structural organization of tissues. Here are the three main roles of cadherin in cell-cell adhesion:
Role of Cadherins in Cell-Cell Adhesion
1. Strong Cell-Cell Adhesion (Direct Role):
Cadherins form strong and specific adhesive bonds between adjacent cells by homophilic binding (same cadherin type binds with the same cadherin type on another cell). This selective binding creates tight and stable junctions that prevent cells from pulling apart, especially in tissues that undergo mechanical stress, such as skin or cardiac muscles. The strength and specificity of cadherin-mediated adhesion help in maintaining tissue organization.
2. Linking to the Cytoskeleton:
In addition to forming cell-cell adhesions, cadherins are connected to the cytoskeleton, particularly the actin filaments in adherens junctions. This interaction helps cells maintain their shape and resist external mechanical forces. In desmosomes, cadherins link to intermediate filaments like keratin, providing further structural support and resistance to mechanical stress.
3. Maintaining Tissue Architecture and Polarity
Although slightly broader, this function still falls under cell adhesion. By forming stable junctions between neighboring cells, cadherins help in defining tissue boundaries and maintain the polarity of epithelial cells. This ensures that cells know which side is the basal side and which is the apical, which is crucial for tissue functioning. Cadherins also play a role in tissue morphogenesis during embryonic development through organized cell adhesion.
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