Cell Junction

What is Cell junction? Cell junctions (or intercellular bridges) are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. Types of cell Junction • Occluding junctions seal cells together in an epithelium in a way that prevents even small molecules from leaking from one side of the sheet to the other. • Anchoring junctions mechanically attach cells (and their cytoskeletons) to their neighbors or to the extracellular matrix. • Communicating junctions mediate the passage of chemical or electrical signals from one interacting cell to its partner.

Tight Junction What is Tight Junction?

• Tight junctions are areas where the membranes of two adjacent cells join together to form a barrier. • The cell membranes are connected by strands of transmembrane proteins such as claudins and occludins. • Tight junctions bind cells together, prevent molecules from passing in between the cells, and help to maintain the polarity of cells.

LOCATION  These structures are found on the epithelium cells that form the internal lining of the body.

 Numerous and highly complex tight junctions are usually found in the epithelial lining of the distal convoluted tubules, the collecting duct of nephrons, the blood brain barrier, and the part of the bile duct that transverses the liver. These linings are thus given the name "tight epithelia".

 Relatively fewer number and less complex tight junctions are present on the epithelial lining of the proximal tubules of the kidney. These linings are called "leaky epithelia A. Structure • Tight junction (TJ) are zipper is like. • Known as occluding junction. • It creates a small zone that occludes the extracellular space (the space between cells).This is why tight junctions are also called zonula occludens. • Composed of numerous important branching network of proteins: • Occludins - maintain the barrier between adjacent cells. Claudins - form the backbone of tight junction strands. Junctional adhesion molecules (JAMs) are immunoglobulin (antibody) proteins - seal the intercellular space between two cells. Zonula occludens (ZO) (proteins) - link the tight junction to each cell’s internal skeleton (cytoskeleton). FIG: STRUCTURE OF TIGHT JUNCTION

Tetraspan proteins contain four membrane-spanning domains; these include proteins like occludins, claudins, and tricellulins. Single-span transmembrane proteins include Junctional Adhesion Molecules (JAMs). Functions of Tight Junctions • The physiological properties of tight junctions depend upon the claudin types expressed. • Some claudins are classified as barrier builders, while others are classified as pore formers. Claudins-1, -3, -4, -8, -11, -14 and -19 -decrease permeability, acting as ‘tightening’ claudins. • Some mediate permeability in a charge- or ion-selective manner. Claudins-2 and -10b display cation-selectivity Claudin-10a increases permeability to small anions. claudin 16-mediated ca2+ and Mg2+ reabsorption in the renal tubule claudin 2- and 15-mediated Na+ recycling, which is essential for Na+- dependent nutrient absorption (Na+-glucose co-transport). A role in paracellular ion transport 1. The barrier function of tight junctions plays a vital role in maintaining the homeostasis within various organ systems. In some cases, tight junctions provide a selectively permeable intercellular space. The digestive tract or kidneys, where the intestines and nephrons possess segment- specific permeability within the tubular epithelia that allows for the absorption of nutrients, or clearance of waste respectively. In each case, function is dependent on the different claudins that constitute tight junctions at these sites. In other cases, tight junctions ensure a relatively impermeable barrier is established. • Tight junctions that exist within the brains endothelial cells maintain Blood-brain- barrier, which separates the neuronal layers of the brain from the systemic circulation. • Blood-retinal barriers regulate intraocular microenvironment and are formed by tight junctions within the retinal capillary endothelial cells and retinal pigment epithelial cells. • Skin and bladder epithelia. • Dysregulation of the barrier function at distinct regions are known to lead to pathological states: neuroinflammation 2. Maintaining Cell Polarity • The dense network of tight junction strands along the apical region acts a fence to prevent the mixing up of components between the apical and basolateral surfaces. • This is essential for the structural and functional differentiation of the two domains and ultimately leads to cell polarity • . Tight junction components, such as the junctional adhesion molecules, also contribute to cell polarity by interacting with Par3/Par6/a-PKC polarity complexes, thereby retaining key cell polarity proteins within the apical domains. A loss of cell polarity is known to lead to cancer properties within the cell. Furthermore, disrupted regulation of tight junction formation may also impair their overall function.

Gap Junction

DEFINITION • • Gap junctions are a type of cell junction in which adjacent cells are connected through protein channels. • These channels connect the cytoplasm of each cell and allow molecules, ions, and electrical signals to pass between them. • Gap junctions are found in between the vast majority of cells within the body because they are found between all cells that are directly touching other cells. LOCATION • Gap junctions are only found in animal cells • Channels called plasmodesmata connect plant cells. STRUCTURE • In vertebrate cells, gap junctions are made up of connexin proteins. • The cells of invertebrates have gap junctions that are composed of innexin proteins, which are not related to connexin proteins but perform a similar function. • Groups of six connexins form a connexon, and two connexons are put together to form a channel that molecules can pass through. • Other channels in gap junctions are made up of pannexin proteins. Relatively less is known about pannexins; they were originally thought only to form channels within a cell, not between cells. • Hundreds of channels are found together at the site of a gap junction in what is known as a gap junction plaque. A plaque is a mass of proteins.

STRUCTURE OF GAP JUNCTION

Plasmodesmata (singular: plasmodesma) • are microscopic channels which traverse the cell walls of plant cells and some algal cells • enabling transport and communication between them. FUNCTION • The main function of gap junctions is to connect cells together so that molecules may pass from one cell to the other. • This allows for cell-to-cell communication, and makes it so that molecules can directly enter neighboring cells without having to go through the extracellular fluid surrounding the cells. • Gap junctions are especially important during embryonic development, a time when neighboring cells must communicate with each other in order for them to develop in the right place at the right time. If gap junctions are blocked, embryos cannot develop normally. • Gap junctions make cells chemically or electrically coupled. This means that the cells are linked together and can transfer molecules to each other for use in reactions. Electrical coupling occurs in the heart, where cells receive the signal to contract the heart muscle In neurons, neurotransmitters are released through it. • When a cell starts to die from disease or injury, it sends out signals through its gap junctions. These signals can cause nearby cells to die. This is called the “bystander effect.

STRUCTURE OF GAP JUNCTION

GAP JUNCTION IN NERVE FIBRE

DESMOSOMES

Definition • Desmosomes are a type of anchoring junction in animal tissues that connect adjacent cells. • Anchoring junctions are button-like spots found all around cells that bind adjacent cells together.

• Desmosomes have intermediate filaments in the cells underneath that help anchor the junction. • Desmosomes, also termed as maculae adherentes, can be visualized as rivets through the plasma membrane of adjacent cells. • Intermediate filaments composed of keratin or desmin are attached to membrane- associated attachment proteins that form a dense plaque on the cytoplasmic face of the membrane. • Cadherin molecules form the actual anchor by attaching to the cytoplasmic plaque, extending through the membrane and binding strongly to cadherins coming through the membrane of the adjacent cell. Desmosome Structure • Desmosomes are composed of desmosome-intermediate filament complexes (DIFC), which is a network of cadherin proteins, linker proteins and keratin intermediate filaments. • The extracellular core region, approximately 34 nm in length, contains desmoglein and desmocollin, which are in the cadherin family of cell adhesion proteins. • Both have five extracellular domains, and have calcium-binding motifs.

• Extracellular calcium helps form the cadherin adhesion by allowing the cadherin extracellular domain on desmoglein and desmocollin to become rigid. • Desmoglein and desmocollin have a single pass transmembrane region plus an intracellular anchor to secure its position in the cell membrane. Desmogleins and the desmocollin Dsc "a" form contain an intracellular cadherin domain, which binds to plakoglobin. • The outer dense plaque, which is about 15–20 nm in length, contains the intracellular ends of desmocollin and desmoglein, the N-terminus side of desmoplakin, and the armadillo family of mediatory proteins plakoglobin and plakophilin. • Plakoglobin has 12-arm repeats with a head and tail structure. Plakophillins have 9-arm repeats, and exist in 2 isoforms: a shorter "a" form and longer "b" form. • The inner dense plaque, also about 15–20 nm in length, contains the C-terminus end of desmoplakin and their attachment to keratin intermediate filaments. Desmoplakin is the most abundant part of the desmosome, as it operates as the mediator between the cadherin proteins in the plasma membrane and the keratin filaments.

FUNCTION 1. Desmosomes are intercellular junctions that provide strong adhesion between cells. Because they also link intracellularly to the intermediate filament cytoskeleton, they form the adhesive bonds in a network that gives mechanical strength to tissues. 2. They play important role to maintain mechanical stress 3. Providing stability and integrity to the tissue structure by providing sites of attachment for cytoskeleton intermediate filaments. 4. It plays important role in maintaining cell-signaling pathways. 5. It also helps in tissue morphogenesis, development and differentiation.