FUNBIO 7 Cytoskeleton and Cell Junctions 2024 PDF

Fundamentals of Human Biology FUNBIO.7 Cell Ultrastructure: Centrioles, Cilia, Cell Junctions P r o f Wa r r e n T h o m a s DAT E: 9 th Oc t ob e r 2 0 2 4 Learning outcomes At the end of this lecture, the learner will be able to Explain the importance of the cytoskeleton in the cell Descri...

Fundamentals of Human Biology FUNBIO.7 Cell Ultrastructure: Centrioles, Cilia, Cell Junctions P r o f Wa r r e n T h o m a s DAT E: 9 th Oc t ob e r 2 0 2 4 Learning outcomes At the end of this lecture, the learner will be able to Explain the importance of the cytoskeleton in the cell Describe in detail the molecular structure and the function of microtubules, microfilaments and intermediate filaments differentiating clearly between these structures. Describe the microtubular structure of centrioles in the animal cell. Explain the role of centrioles in cell division and centrosome formation. Show the origin of the microtubular spindle fibres from gamma-tubulin rings in the centrosome. Discuss the significance of the intercellular junctions noting the three main types. Describe the structure and function of adhering, gap and tight junctions. 2 Cytoskeleton  Cytoskeleton Animal cells maintain their shape by the existence of a three-dimensional network in the cytoplasm called the cytoskeleton This consists of a system of tubular and filamentous structures Three elements make up this system: 1. Microtubules 2. Microfilaments 3. Intermediate filaments All are readily assembled from soluble pools of cytoplasmic proteins Cytoskeleton  Microtubules Microtubules - Structure Appear to exist as hollow cylinders, 25 to 30nm diameter They are composed of 13 subunits in a left-handed helix Each subunit is a heterodimer of two proteins - and ß-tubulin Protofilament The heterodimer runs parallel to the long axis of the tubule They are the thickest filaments and are rigid They have a + and a - end https://www.youtube.com/watch?v=ZpEKOH4LBAc  Microtubules Function Microtubules have structural and functional roles in the cell: 1. They form the axoneme of the cilium and flagellum 2. They form the components of the centrioles 3. They also form the spindle fibres of cell division 4. Associated with intracellular movement in the axons of nerve cells Microtubules Motile Non- Motile 9+2 9+0 Airway Primary Cilium Sperm flagellum epithelial cell Kidney  Cytoskeleton - Microfilaments Also known as Actin filaments Apart from the microtubules more solid filaments may be seen under high EM magnifications In cross section they could be confused with small ribosomes though they are only 33% of their diameter https://www.youtube.com/watch?v=pyEVmWLOePw  Cytoskeleton - Microfilaments Structure These are solid filaments, 5-7nm diameter Largely formed of the protein actin They are found in most animal cells and in some plant cells They are concentrated in networks or bundles just below the plasma membrane Intestinal microvilli are produced by the microfilaments Microfilaments  Intermediate Filaments Structure Heterogeneous in composition Any given cell will have more than one type One type of filament usually predominates Five main types based on the protein involved Type I & II- keratins divided into acidic and basic types Type III - vimentin-like proteins, found in cells of mesodermal origin Type IV - neurofilaments, found in nerve axons Type V - nuclear laminins - forming the nuclear lamina  Intermediate Filaments File:Intermediate filament.svg This is a separate system of rope-like filaments found in most cells Size intermediate to actin filaments and microtubules Form solid filaments between 7-11nm in diameter Non-alpha-helical (globular) domain at the N and C-termini which surrounds the alpha-helical rod domain. Basic building block is parallel dimer. Dimer is formed through interaction of the rod domain to form a coiled coil Intermediate Filaments  Centrioles Characteristically found in all animal cells and ciliated plant cells Usually found in the cytoplasm in an area near the nucleus Often associated with the Golgi apparatus This area is called the Microtubule Organizing Centre  Centrioles - Structure Usually found as two cylindrical structures at right angles to one another, Typically one pair per cell during interphase Composed of 9 sets of triplets arranged as a cylinder - Tubulin Called a 9x3 structure (9+0 structure) of Triplet microtubules  Centrioles - Structure In each triplet: Set A, is closest to the centre and is a complete microtubule Set B and C share portions of their walls ‘9 - 3’ configuration  Centrioles - Structure Cartwheel: At one end of the centriole there is a so- called cartwheel structure Additional material that protrudes from the outer surface at proximal end of a mature centriole Fibrous structures connecting the two centriole cylinders  Centrioles - Function Prior to cell division the centrioles replicate and move to the opposite poles of the cell Most cells’ centrioles duplicate by the growth of new daughter centriole at right angles to the 'old' centriole One new centriole and one old centriole Form areas known as centrosomes  Centrosomes The centrosome is the main microtubule organizing centre of the cell Composed of: Two orthogonally arranged centrioles Pericentriolar material (purple). Contains proteins responsible for microtubule nucleation and anchoring  Centrosomes Because microtubules radiate from the centrosome area it was thought that the centrioles were involved in organizing the microtubules Microtubules originate from -tubulin rings in the centrosomal matrix (Distal appendages) not from the centrioles Each -tubulin ring serves as the nucleation site (starting point) for one microtubule  Centrosomes An aster of microtubules (fibres) extends to form the visible spindle fibres of cell division Some spindle fibres bind to the chromosomes at the centromere Cell Junctions  Cell Junctions Most cells in tissues are attached to other cells Only a small number of cells in the body, such as the blood cells, lead relatively independent lives The cells in tissues are separated by an intercellular space of between 20-30nm wide But in some areas of specialized intercellular junction more direct contact is maintained between adjacent parts of the two membranes Three types of cell junction occur: 1. Adhesion Junctions (Adherens and Desmosome Junctions) 2. Tight Junctions 3. Gap Junctions  Cell Junctions Adhesion/ Adhering Junctions: Principal mechanical interlinks between cells Strong junctions that tightly bind adjacent epithelial cells, such as those found in outer layer of mammalian skin Two types: Desmosomes Adherens junctions The intercellular space is normal (30nm) but filled with transmembrane proteins called cadherins  Cadherins Cadherins form links to cytoplasmic structures Link membrane to cytoskeleton 3 types E-cadherin – epithelial N-cadherin – neuronal P-cadherin – placental Cadherins are lost in cancer & metastases  1. Adherens (Anchoring) Junctions The cadherin attachment is via linker proteins to actin microfilaments in the cytoplasm. Serve as a bridge connecting the actin cytoskeleton of neighbouring cells through direct interaction  2. Desmosomes Disc-like plaques in cytoplasm, 20nm thick, 0.2-0.3µm diameter There are two types of desmosome: Spot desmosomes (Macula adherens), which are like spot rivets These connect cells to each other via intermediate filaments Hemidesmosomes connect the basal surface of epithelial cells to the underlying basal lamina The transmembrane linker proteins here are different - integrins. Desmosomes Hemi-desmosome (Integrins)  Gap Junctions Involved in the interchange of small inorganic ions and molecules between adjacent cells. The intercellular space is reduced to between 2-4nm Hexagonal Hexagonal array of proteins in each membrane array The transmembrane proteins are called connexins Connexin  Gap Junctions Each array is aligned to an array in the opposing face This results in the formation of a hydrophilic channel with a pore size of about 1.5nm diameter Gap junctions are associated with the intercalated discs in cardiac muscle where they facilitate the transmission of electrical impulses between cardiac muscle cells. Hydrophilic channel  Tight Junctions In the cells lining the mammalian intestine, the kidney and those lining the urinary bladder the plasma membranes form close connections These appear as a fusion of the plasma membranes of two cells These are called tight junctions (zonula occludens)  Tight Junctions Form a belt-like structure of branching sealing strands Network of strands are thought to be transmembrane proteins in the adjoining membranes forming interconnections Function is to seal off the intercellular space, forming almost impermeable barrier Have a role in the maintenance of concentration gradients between the exterior lumen and the intercellular space Plasma Protein Connexin Rows of filaments Plasma molecules membranes tight junction Channel membranes proteins Desmosome Intercellular Intermediate Intercellular space filaments c a space Disc of dense b protein material Pemphigus Vulgaris Involves the Desmosomes Pemphigus vulgaris is an autoimmune, intraepithelial, blistering disease affecting the skin and mucous membranes. Autoantibodies target proteins of the desmosome leading to disruption of cell adhesion. Adjacent layers of the skin can pull apart and allow abnormal movements of fluid within the skin, resulting in blisters and other tissue damage. A potentially life-threatening disease, it has a mortality rate of approximately 5-15%.  Reading Chapters 4 & 5 Solomon 11th edition p98-102, 125-128 F O R M O R E I N F O R M AT I O N P L E A S E C O N TA N T P r o f Wa r r e n T h o m a s EMAIL: wathomas @rc si -mu b.c om