BIOC 601 Molecular Aspects of Cell Biology Lecture 1 PDF

BIOC 601 MOLECULAR ASPECTS OF CELL BIOLOGY Professor Neils Ben Quashie + others  Course Content This course will focus on assembly and functions of macromolecules and signal transduction pathways/ cell-to-cell communication: Self-assembly of macromolecules and dynamic structu...

BIOC 601 MOLECULAR ASPECTS OF CELL BIOLOGY Professor Neils Ben Quashie + others  Course Content This course will focus on assembly and functions of macromolecules and signal transduction pathways/ cell-to-cell communication: Self-assembly of macromolecules and dynamic structure of the cytoskeleton; The role of spectrin, actin, microtubules and intermediate filaments in the formation of the cytoskeleton; Principles of membrane transport, transport proteins, active and passive transport; biological membrane transport systems; Ion channels and the electrical properties of membranes, membrane potential; Mechanism of cell communication, receptor-ligand interaction, super-families of membrane receptors and their ligands, intracellular receptors and their ligands, slow and rapid signalling; Gap junction communications; Signalling through G-protein coupled receptors; inositol phospholipid signalling pathway Course Description The course shall equip students to gain understanding in how the assembly of macromolecules in the cell membrane define the structure and function of the cell. Students will also gain insights into cell-cell communication and the consequences of abnormalities in cell-cell communication. These concepts would make the students appreciate how the integrated components and molecular mechanisms of the cell make it function as a living unit  Aim and Objective Aim To enable students to understand the functional assembly of macromolecules in cell membranes and gain in-depth insights on cell- cell communication. Course Objectives  Provide students with an in-depth understanding of the mechanisms of cell-cell communication and the diverse forms of cell signalling.  Expose students to abnormal signalling pathways that have been implicated in disease conditions. Enable students understand the relevance of neurotransmission pathways in cell signalling Teaching strategy Mode of Delivery Didactic lectures Team-based learning Problem-based learning Group discussions and assignments Learning Outcomes At the end of the course, students should be able to: Explain mechanisms of cell-cell communication and the diverse forms of cell signalling. Explain abnormal signalling pathways that leads to Graves’ disease, cholera, whooping cough, Myasthenia gravis and cell transformation. Explain neurotransmitters, receptors and transport proteins in signalling at synapses Reading List Alberts, B., Hopkin, K. & Johnson, A. D. (2019). Essential cell biology (5th ed.). W.W. Norton. Cooper, G. & Adams, K. (2022). The cell: A molecular approach. United States: Oxford University Press, Incorporated. Karp, G., Iwasa, J. & Marshall, W. F. (2020). Karp’s Cell and Molecular Biology (9th ed.). John Wiley & Sons Inc. Lodish, H. F., Berk, A., Kaiser, C., Krieger, M., Bretscher, A., Ploegh, H. L., Martin, K. C., Yaffe, M. B. & Amon, A. (2021). Molecular cell biology (9th ed.). Macmillan Learning Plopper, G. & Ivankovic, D. B. (2020). Principles of Cell Biology (3rd ed.). Jones & Bartlett Learning. Roelen, B. A. J. & Rodrigues, G. (2020). Concepts and Applications of Stem Cell Biology: A Guide for Students (2nd ed.). Springer International Publishing.  Focus of lectures Self-assembly of macromolecules and dynamic structure of the cytoskeleton; The role of spectrin, actin, microtubules and intermediate filaments in the formation of the cytoskeleton; Principles of membrane transport, transport proteins, active and passive transport; biological membrane transport systems; This course will focus on assembly and functions of macromolecules and signal transduction pathways/ cell-to-cell communication: Self-assembly of macromolecules and dynamic structure of the cytoskeleton; The role of spectrin, actin, microtubules and intermediate filaments in the formation of the cytoskeleton; Principles of membrane transport, transport proteins, active and passive transport; biological membrane transport systems; Ion channels and the electrical properties of membranes, membrane potential; Mechanism of cell communication, receptor-ligand interaction, super-families of membrane receptors and their ligands, intracellular receptors and their ligands, slow and rapid signalling; Gap junction communications; What is a cytoskeleton? It is a network of interlinking protein filaments present in the cytoplasm of all cells including bacteria and archaea, spanning from the nucleus to the cell membrane It is composed of the same proteins in all organisms It consist of three main components: Microfilaments Intermediate filaments Microtubules, Present in eukaryotes and prokaryotes  Functions of the cytoskeleton Cell shape and mechanical support: The cytoskeleton provides the cell with a defined shape and helps it maintain its structural integrity. It also allows the cell to resist external forces. The cytoskeleton maintains the positions of numerous cellular organelles. Cell movement: The cytoskeleton is responsible for cell movement, including the movement of cilia and flagella. It also allows cells to change their shape during processes such as cell division and migration. Intracellular transport: The cytoskeleton plays a critical role in the transport of materials within the cell. Microtubules serve as tracks for the movement of organelles and other cellular components, while microfilaments and intermediate filaments anchor these structures in place. Cell division: The cytoskeleton is essential for cell division, helping to organize and separate the chromosomes during mitosis. Signal transduction: The cytoskeleton plays a role in signal transduction pathways, which are essential for cell communication and coordination. The cytoskeleton facilitates the transfer of intercellular communication impulses. Vacuoles Formation: It aids in the development of vacuoles. Cilian and Flagella: In some cells, it generates appendage-like protrusions, such as cilia and flagella Involved in muscle contraction (through the microfilament) Others  Components of the cytoskeleton Microtubules: Microtubules are hollow rods that primarily support and form the cell and serve as “routes” for organelle movement. Typically, microtubules are present in all eukaryotic cells. They vary in length and have a diameter of approximately 25 nm (nanometers). Microfilaments: Involved in muscular contraction, microfilaments or actin filaments are thin, rigid rods. Microfilaments are particularly common in muscle cells. Comparable to microtubules, they are found in all eukaryotic cells. Microfilaments consist mostly of the contractile protein actin and have a diameter of up to 8 nm. They are also involved in organelle mobility. Intermediate filaments: Microfilaments and microtubules are supported by intermediate filaments, which can be plentiful in many cells. Intermediate filaments also give microfilaments and microtubules with structural support. These filaments are responsible for the formation of keratins in epithelial cells and neurofilaments in neurons. These are 10 nanometers in diameter. Role of spectrin in the formation of cytoskeleton Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. The hexagonal arrangements are formed by tetramers of spectrin subunits associating with short actin filaments at either end of the tetramer These short actin filaments act as junctional complexes allowing the formation of the hexagonal mesh  Function of Spectrin Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure In animals, spectrin forms the meshwork that provides red blood cells their shape Some evidence for the role of spectrins in muscle tissues exist Similarly, spectrin plays a role in Drosophila neurons. Knock-out of a or ß spectrin in D. melanogaster results in neurons that are morphologically normal but have reduced neurotransmission at the neuromuscular junction In animals, spectrin forms the meshwork that provides red blood cells their Shape A mutation in ß spectrin in C. elegans results in an uncoordinated phenotype in which the worms are paralysed and much shorter than wild- type  The role of Actin in the formation of cytoskeleton Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton It is found in essentially all eukaryotic cells Present at a concentration of over 100 µM; its mass is roughly 42 kDa, with a diameter of 4 to 7 nm  Functions of Actin Actin participates in many important cellular processes, including muscle contraction, cell motility, cell division and cytokinesis, vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape Actin contributes to processes such as the intracellular transport of vesicles and organelles as well as muscular contraction and cellular migration It plays an important role in embryogenesis, the healing of wounds, and the impassivity of cancer cells A large number of illnesses and diseases are caused by mutations in alleles of the genes that regulate the production of actin or of its associated protein Others The role of microtubules in the formation of cytoskeleton Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm 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 Function of microtubles Microtubules play an important role in a number of cellular processes They are involved in maintaining the structure of the cell and, together with microfilaments and intermediate filaments, they form the cytoskeleton They also make up the internal structure of cilia and flagella They provide platforms for intracellular transport and are involved in a variety of cellular processes, including the movement of secretory vesicles, organelles, and intracellular macromolecular assemblies They are also involved in cell division (by mitosis and meiosis) and are the main constituents of mitotic pindles, which are used to pull eukaryotic chromosomes apart Others Role of intermediate filaments in the Formation of cytoskeleton Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates All IF proteins appear to have a central alpha-helical rod domain that is composed of four alpha-helical segments (named as 1A, 1B, 2A and 2B) separated by three linker regions There are about 70 different human genes coding for various intermediate filament proteins  Functions of intermediate filaments Provides tensile strength to the cell These filaments comprise the central scaffold of cells, imparting structural stability to the three-dimensional intracellular architecture  What is a living cell? A cell is the smallest unit that can live on its own and that makes up all living organisms and the tissues of the body Most cells have one or more nuclei and other organelles that carry out a variety of tasks Generally a cell has three main parts: Cell membrane Nucleus Cytoplasm  Nature of a cell Most plant and animal cells are only visible under a light microscope, with dimensions between 1 and 100 micrometres Electron microscopy gives a much higher resolution showing greatly detailed cell structure Organisms can be classified as unicellular (consisting of a single cell such as bacteria) or multicellular (including plants and animals) The smallest known cells are a group of tiny bacteria called mycoplasmas: are spheres as small as 0.2 μm in diameter (1μm = about 0.000039 inch) Fine structure of an animal cell  Plant Cells vs. Animal Cells Similarities: Plant and animal cells are both eukaryotic cells (possess a defined nucleus and membrane-bound organelles) They share many common features, such as a cell membrane, nucleus, mitochondria, Golgi apparatus, endoplasmic reticulum, ribosomes etc. Differences Plant cells have a cell wall that surrounds the cell membrane, whereas animal cells do not. Plant cells possess two organelles that animal cells lack: chloroplasts and a large central vacuole. These additional organelles allow plants to form an upright structure without the need for a skeleton (cell wall and central vacuole), and also allow them to produce their own food through photosynthesis (chloroplasts)  Cell types Cells are of two types: Eukaryotic contains a nucleus Prokaryotic cells do not have a nucleus, but a nucleoid region Prokaryotes are single-celled organisms Eukaryotes can be either single-celled or multicellular This image is from the Science