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Week 8 (2) HISTOPATHOLOGY (BMS4470A) CYTOPLASM – Part 2 Dr. Merin Thomas [email protected] Office hours : Tuesday & Thursday – 1.00pm to 3.00pm Learning Objectives...

Week 8 (2) HISTOPATHOLOGY (BMS4470A) CYTOPLASM – Part 2 Dr. Merin Thomas [email protected] Office hours : Tuesday & Thursday – 1.00pm to 3.00pm Learning Objectives Cell differentiation The plasma membrane Cytoplasmic organelles The cytoskeleton Inclusions CYTOPLASMIC ORGANELLES Inside the cell membrane, the fluid cytoplasm (or cytosol) bathes metabolically active structures called organelles, which may be membranous (such as mitochondria) or non-membranous protein complexes (such as ribosomes and proteasomes). Most organelles are positioned in the cytoplasm by movements along the polymers of the cytoskeleton, which also determines a cell’s shape and motility. Cytosol also contains hundreds of enzymes, such as CYTOPLASMIC ORGANELLES - Ribosomes Ribosomes are macromolecular machines, about 20 × 30 nm in size, which assemble polypeptides from amino acids on molecules of transfer RNA (tRNA) in a sequence specified by mRNA. A functional ribosome has two subunits of different sizes bound to a strand of mRNA. Maybe bound to a membrane or free in the cytosol Engage in protein synthesis Bound ribosomes: produce proteins that are secreted, incorporated into plasma membrane, CYTOPLASMIC ORGANELLES – Endoplasmic Reticulum The cytoplasm of most cells contains a convoluted membranous network called the endoplasmic reticulum (ER). It is a network (reticulum) that extends from the surface of the nucleus throughout most of the cytoplasm and encloses a series of intercommunicating channels called cisternae (reservoirs). The ER is a major site for vital cellular activities, including biosynthesis of proteins and lipids. CYTOPLASMIC ORGANELLES – Endoplasmic Reticulum CYTOPLASMIC ORGANELLES – Endoplasmic Reticulum CYTOPLASMIC ORGANELLES – Golgi Apparatus The dynamic organelle called the Golgi apparatus, or Golgi complex, completes posttranslational modifications of proteins produced in the RER and then packages and addresses these proteins to their proper destinations. The organelle was named after histologist Camillo Golgi who discovered it in 1898. The Golgi apparatus consists of many smooth membranous saccules, some vesicular, others flattened, but all containing enzymes and proteins being processed. CYTOPLASMIC ORGANELLES – Golgi Apparatus CYTOPLASMIC ORGANELLES – Lysosomes Lysosomes are sites of intracellular digestion and turnover of cellular components. Spherical-shaped membrane-bound organelles formed from the Golgi apparatus Lysosomes (Gr. lysis, solution, + soma, body) contain about 40 different hydrolytic enzymes and are particularly abundant in cells with great phagocytic activity (e.g., macrophages, neutrophils). They digest microbes or materials (e.g., ingested by the cell, worn out cellular components, or the entire CYTOPLASMIC ORGANELLES – Lysosomes CYTOPLASMIC ORGANELLES – Mitochondria Mitochondria (Gr. mitos, thread, + chondros, granule) are double membrane-enclosed organelles with arrays of enzymes specialized for aerobic respiration and production of adenosine triphosphate (ATP) Synthesize most ATP during aerobic cellular respiration by digestion of fuel molecules (e.g., glucose) in the presence of oxygen CYTOPLASMIC ORGANELLES – Mitochondria CYTOPLASMIC ORGANELLES – Mitochondria Mitochondrial diseases are a group of genetic conditions that affect how mitochondria in the cells produce energy. Can affect almost any part of the body including cells of the brain, nerves, muscles, kidney, heart, liver, eyes, pancreas etc. Mitochondrial diseases are genetic - inherited CYTOSKELETON The cytoplasmic cytoskeleton is a complex array of microtubules, microfilaments (also called actin filaments) intermediate filaments These protein polymers determine the shapes of cells, play an important role in the movements of organelles and cytoplasmic vesicles, and allow the movement of entire cells. Microtubules (MT) and actin microfilaments (MF) can both be clearly distinguished in this TEM, which provides a good comparison of the relative diameters of these two cytoskeletal components. (X60,000) CYTOSKELETON Arrays of microfilaments and microtubules are easily demonstrated by immunocytochemistry using antibodies against their subunit proteins. Actin filaments (red) are most concentrated at the cell periphery. Microtubules (green/yellow) are oriented in arrays that generally extend from the centrosome area near the nucleus into the most peripheral CYTOSKELETON The cytoskeleton contains three types of polymers: 1. Microtubules 25 nm in diameter 2. Actin filaments or microfilaments (5-7 nm) 3. Intermediate filaments (8-10 nm). CYTOSKELETON - Microtubules Microtubules are semi-rigid tubular structures with walls composed of polymerized tubulin heterodimers; Structure is often very dynamic, with steady addition and dissociation of tubulin. Microtubules are important in maintaining cell shape and as tracks for transport of vesicles and organelles by the motor proteins kinesin and dynein. CYTOSKELETON - Microfilaments Microfilaments are short, flexible, highly dynamic filaments of actin subunits, in which changes in length and interactions with binding proteins regulate cytoplasmic viscosity and movement. Myosins are motor proteins that bind and move along actin filaments, carrying vesicles or producing cytoplasmic movement. Movements of cytoplasm produced by actin filaments and myosins are important for endocytosis, cell cleavage after mitosis, and CYTOSKELETON – Intermediate filaments Intermediate filaments are the most stable cytoskeletal component, conferring strong mechanical stability to cells. Intermediate filaments are composed of various protein subunits in different cells; they include vimentin, nuclear lamins, neurofilament proteins, and keratins, which are especially important in epithelial cells. Intermediate filaments (IF) display an average diameter of 8-10 nm, between that of actin filaments and microtubules, and serve to provide mechanical strength or stability to cells. Glial fibrillary acidic protein (GFAP) INCLUSIONS Unlike organelles, inclusions are not metabolically active and are primarily storage sites, such as lipid droplets, glycogen granules, pigment granules, or residual bodies (also called lipofuscin). INCLUSIONS Cytoplasmic inclusions contain accumulated metabolites or other substances, but unlike organelles have no metabolic activity. Most inclusions are transitory structures not enclosed by membrane. Commonly seen inclusions include the following: Lipid droplets Glycogen granules Pigmented deposits INCLUSIONS Lipid droplets, accumulations of lipid-filling adipocytes (fat cells) and present in various other cells. Glycogen granules, aggregates of the carbohydrate polymer in which glucose is stored, visible as irregular clumps of Periodic Acid–Schiff (PAS) positive or electron dense in several cell types, notably liver cells INCLUSIONS Pigmented deposits of naturally colored material, including melanin, dark brown granules which in skin serve to protect cells from ultraviolet radiation lipofuscin, a pale brown granule found in many cells, especially in stable nondividing cells (eg, neurons, cardiac muscle); and hemosiderin, a dense brown aggregate of denatured ferritin proteins Lipid droplets Glycogen granules Pigmented deposits REFERENCES Mescher, A. L. (2018). Junqueira’s Basic Histology Text and Atlas, FIFTEENTH. In McGraw-Hill Education eBooks. http://125.212.201.8:6008/handle/DHKTYTHD_123/5904

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