Dr Hiba CBC+SVT E Cytology Part I PDF

B1100- CYTOLOGY SVT-CBC 2024-2025 Dr. Hiba NOUREDDINE-FAKIH Lebanese University- Faculty of 1 Sciences V  B1100 Cytology Histology Dr Hiba NOUREDDINE Dr Wissam JOMAA Cytology: science which studies the cell His...

B1100- CYTOLOGY SVT-CBC 2024-2025 Dr. Hiba NOUREDDINE-FAKIH Lebanese University- Faculty of 1 Sciences V  B1100 Cytology Histology Dr Hiba NOUREDDINE Dr Wissam JOMAA Cytology: science which studies the cell Histology: science which studies the tissues 2  B1100 = 60 hours 30 h 30 h Cytology Histology 10 hours = 1 credit B1100= 6 credits Final exam is noted / 100 pts: 50 pts cytology 50 pts hystology ! This note will be multiply by 6 which is the nb of credits of this course 3 INTRODUCTION 4 All living beings are made up of microscopic elements: The cells. In humans, there are several billions of cells. Cytology: science which studies the cell Histology: science which studies the tissues Small molecule virus bacteria animal cell plant cell Electron microscope Optical microscope 5  Cytology = Cell biology = Study of the cell Morphology = Study of cell life, Form and structure of Continuity and function cells Chemical composition = components & molecules constituting the cells 6  There are two worlds: Inert Living These two worlds have the same basic chemical elements what differ are the percentage & distribution of these elements The cell belongs to the living world 7  The cell is characterized by : 1. organization 2.functional properties a- Living beings a- Nutrition Assimilation / dissimilation b- Organelles b- Reproduction c- Molecular and chemical components c- Irritability 8 1. About organization: It occurs at  levels: 1.a- Living beings: 1organism = set of  systems (respiratory, digestive,……) 1 system = set of  organs ( lung, heart,…..) 1 organ = set of  tissues ( muscular, epithelial,…..) 1 tissue = set of  cells. The cell is the morphological unit of an organism 9 What is the origin of a cell? = egg cell = fertilization = Fusion between gamete male & gamete female. A cell comes from a preexistant cell & there is no life outside the cell The cell is the functional unit of an organism Hence, The well-known definition: The cell is the morphological and functional unit of an organism 10 Therefore, the cell is :  a morphological unit: supports biological activities  a reproduction unit: development or repair of tissues and organs  a unit of information: contains the hereditary information  a functional unit: ensures the achievement of biological activities necessary for life 11 1.b-Organelles: The cell (especially eukaryotic cell) has an intracellular organization. It contains different organelles (ER, Golgi, mitochondria,……). Each organelle has a particular role. 1.c- At molecular level: The cell is composed of minerals & organic elements. 12 2. About functional properties: - The cell belongs to the living world. - All living things have common functional properties that are: 2.a- Nutrition : Each cell, to stay alive, must exchange with the exterior. This exchange is important for the renewal of molecules and the cell turnover. We distinguish 2 phenomenon: Assimilation & dissimilation 13  Assimilation: Is the capacity of cell to transform exterior nutritive molecules into intracellular components.  Dissimilation: is a phenomenon by which a substance leaves the cell and then it stops its function. 2.b- Reproduction : Every living beings are able to reproduce, this allows he continuity of species. There are two types of reproduction: - Asexual reproduction for unicellular - Sexual reproduction for multicellular 14 2.c- Irritability : Is the capacity of cells to respond to stimuli (physical, chemical or physiological) It is more developed in animals because of nervous & muscular systems. 15  Chapter I: Morphological study # Shapes, dimensions & structures * PROKARYOTES / EUKARYOTES = BACTERIA / ANIMALS & PLANTS * VIRUSES 16 Pro = Befor (without) Karyon = nucleus - 1 Circular DNA - Without nucleus - Without Organelles (except some ribosomes) 17  There are two major groups of prokaryotes: Archaebacteria (ancient bacteria): Live in extreme conditions of temperature, pH and salinity like ocean bottom, Dead sea…. Halophiles, thermoacidophiles,…… 18  Eubacteria (true bacteria): More common forms. Most of them live in mild conditions that are quite similar to those required for eukaryotes. They can be found in soil, water, living organism…… Cyanobacteria, Gram+ & Gram– bacteria, mycoplasma, green photosynthetic bacteria….. 19 A. Overview of the bacteria: - Are the most abundant and simple creatures - Some are pathogenic - many useful in # areas Industry (acetone production) Vitamins Antibiotics Ecological (decomposition and recycling of organic matter) Food (milk  yogurt) 20 - Unicellular and autonomous - Asexual reproduction (not by mitosis): * by binary fission in a rich media 21 B. Classification: It depends on # criteria: Requirement of oxygen: 4 types - Strictly aerobic bacteria: can only survive in the presence of oxygen in the air - Strictly anaerobic bacteria: can only survive without oxygen - Facultative aero- anaerobic bacteria: can survive with or without oxygen - Microaerophiles require oxygen at a lower concentration than the concentration in the air. 22  Morphologically: # forms and sizes - Nomenclature of bacteria uses prefixes related to their shape. Bacteria are classified, by shape, into 3 groups: Spiral: spirilla Elongate: Bacillus anthracis, vibrio cholera Spherical: cocci 23 - About sizes of bacteria: Cocci bacteria are about 1mm in diameter. Escherichia coli are elongate (2mm in length). Some bacteria are about 5mm to 10 mm in length (cyanobacteria). However, the average size of bacteria is about 1 to 2mm. 24 There are very small bacteria (0,2 mm in diameter), even smaller than some viruses, named mycoplasma or PPLO: - May be spherical or filamentous - Belong to the class of mollicutes (e.g. Mycoplasma pneumonia). - Cause a number of diseases in human, animals (especially in the respiratory and urogenital tracts) as well as in plants. 25 - Behave as intracellular parasites although they can grow in cell free media and undergo shape changes depending on the composition of medium available to them: polymorphic bacteria Since they lack rigid envelope: they are bounded by a special membrane made up of lipids (including cholesterol) and proteins, but are deprived from cell wall and capsule. - Some mycoplasma are classified as eubacteria, others (e.g. thermoplasma) are classified as archeabacteria. 26 Energy sources : 2 types - Light energy : photosynthetic or phototrophic bacteria - Energy from the degradation of chemical compounds: chimiotrophic bacteria 27 C. Bacterial cell Structure:  Essential components:  Non essential Basic structure present in components: all bacteria, e.g. cell wall Present in some bacteria (except mycoplasma), species, e.g. capsule, cytoplasmic membrane, fimbria, flagella, spores, cytoplasm, genetic plasmids. material. 28  Cytoplasm: - Viscous watery solution or soft gel that contains a variety of organic and inorganic solutes. - It is not compartmentalized: there are no organelles (no mitochondria, no ER, no Golgi, no chloroplasts, no cytoskeleton, no vesicles). - Although no organelles are found in prokaryotes, infoldings of the plasma membrane may occur especially in photosynthetic bacteria forming lamella. These lamella may separate from the membrane and form independent structures named chromatophores. 29 Note that such lamella are not comparable to ER of eukaryotic cells. - Similarly, cyanobacteria have no organelles but they are provided with membrane bounded gaz vacuoles and carboxysomes (complex of enzymes involved in CO2 fixation for photosynthesis). TEM view of cyanobacterium section showing photosynthetic lamella and carboxysomes (dark circles). 30 -Within the cytoplasm of all bacteria there are ribosomes that translate mRNA into proteins. - These ribosomes are different from eukaryotic ribosomes in terms of size and composition. - Ribosomes are free or attached to the plasma membrane, but no ribosome are attached to cytoplamic lamella when they occur. - Cytoplamic bacteria is rich in enzymes, water, mRNA, tRNA... - Also, there are granules that represent stored inorganic and organic compounds such as sulfur, phosphates and carbohydrates, 31 32  Nucleoid: an irregularly-shaped dense region, that contains the genetic material, and it is not wrapped by a membrane. double-stranded DNA molecule, circular and supercoiled chromosome (condensed by specific proteins). Replication, Transcription and translation take place simultaneously in the cytoplasm. 33  In Prokaryotes and certain eukaryotes like yeast, there is an extrachromosomal genetic material called plasmid Double stranded, circular DNA molecule, carry a few genes that confer advantages to the host cell (e.g. genes responsible for resistance to antibiotics). They are indispensable for molecular biology and genetic engineering. 34  Plasma membrane - Enveloped by a cell wall in all species (expect mycoplasma) - It has the same basic structure as that of eukaryotic cell membrane (lipid bilayer) but does not contain sterol (except in mycoplasma). - It contains many proteins with multiple functions (transporters, receptors, respiratory chain proteins, ATP synthase……) 35  The basic structure of PM is that of a phospholipid bilayer (hydrophilic head (hydrophobic Tail Fatty acid PM contains many intrinsic and peripheral proteins 36  37 Note that bacteria do not contain cholesterol - Selective permeability: Molecules move across the membrane - Respiration: the cytochrome and respiratory enzymes are localized in the plasma membrane. - Play an important role in cell division. 38 Mesosomes: - Invagination of plasma membrane. - Attachment site of nucleoid (DNA), probably implicated in replication - Recently considered as artifact of the sample preparation for microscopy analysis Presence of enzymes & elements required for biosynthesis, respiration….. Inability to deform ( no endo & exocytosis) 39  Bacterial cell wall - Rigid structure, determines bacterial shape - Maintains a high internal osmotic pressure (resistance to physical disruption) - Rich in peptidoglycans (glucose and N- acetylglucosamine joined by peptides bridges). - There are 2 types of bacteria wall with # chemical compositions: Gram+ & Gram- 40 41 Gram positive - Have thick layer of peptidoglycan over inner cytoplasmic membrane. Gram negative - The peptidoglycan layer is thinner and is located in periplasmic space). - Contain LPS and porins. 42  Difference Between Gram-Negative and Gram-Positive Bacteria Gram-Negative Gram-Positive Bacteria Bacteria More complex cell Simple cell wall. wall. Thin peptidoglycan Thick peptidoglycan cell wall layer. cell wall layer. Outer No outer lipopolysaccharide lipopolysaccharide wall layer. wall layer. Ex: E. coli Ex: Bacillus subtillis 43 44 45  Capsule - Present in some species of bacteria (Generally for pathogen bacteria) - Organic substances (extracellular polymers of polysaccharides) - Settle outside of the bacterial wall forming a viscous layer. - Cell-cell and cell-support adhesion - Protection against phagocytosis - Contributes to bacterial virulence 46  Flagella: - Many bacteria have one or more flagella - Organs of motility (cellular locomotion) - May be located at one pole of the cell or distributed over the entire cell surface - Composed of 3 parts: a filament, a hook and a basal body: * The filament is a polymer entirely made up of one protein type (flagellin) that forms hollow cylinder. * The hook connects the filament to the basal body which is anchored in the envelope. * The basal body generates flagellum rotation Flagella 47 - The flagellum structures arise from the basal body in the cytoplasm and cross the plasma membrane, the cell wall and capsule when they are present. - Unlike eukaryotic flagella, the bacterial flagellum is naked, not enveloped by extension of the plasma membrane. Cyanobacteria lack flagella. They usually occur as individual cells, as small clusters or colonies or as long filamentous chains. These bacteria are able to move by gliding due to a gelatinous layer that externally covers the cell wall. 49  Pili (Fimbriae): Pilli - Hair like filaments, formed of protein called pillin - Helps cells to adhere surfaces - Transfer of plasmidic DNA from one cell to another (conjugation) - Not implicated in the mobility - Are shorter and thinner than flagella. Flagella 50 51  Endospores: - Members of several bacterial genera are capable of forming endospores under condition of stress or nutritional depletion. - An endospore is a resting cell that is highly resistant to desiccation (drought), heat and chemical stress. - The endospore consists of the bacterial DNA plus a number of cellular structures which are all enveloped by a membrane that is surrounded by special cell wall and coat. - An endospore may resist harsh conditions for tens of years and when the medium is favorable again it germinates and reforms the original bacterium. 52 53 54 Eu = True Karyon = nucleus - Presence of many DNA localized in a particular cellular compartment = nucleus - Organelles & internal 55 membranes Unicellular : Yeast, paramecium, amoeba Pluricellular : animal, plant & human Photoautotrophs (perform photosynthesis), or heterptrophs Larger and more complex than prokaryotic cell. 10< size 3 ‘ sense while the complementary strand is in the 3'-> 5' sense. - The 2 strands are twisted around each other forming a double helix, of 2nm in diameter and whose central axis = hydrogen bonds. - 2 helical grooves (called major & minor grooves) at the surface of the molecule 189 For clarity, the two DNA strands are shown untwisted in this partial chemical structure. Strong covalent bonds link the units of each strand, while weaker hydrogen bonds hold one strand to the other. Notice that the strands are antiparallel, meaning that they are oriented in opposite directions. 190  10 base pairs (bp) per twist on each full turn of the helix 2.37 nm The helix is right-handed, it turnes in clockwise direction = B form 191  Some characteristics of DNA: - All components are in equimolecular proportion: n desoxyriboses = n H3PO4 = bases - A / T = C / G = 1 (Chargaff’s rule) -A+G=C+T - (A + T) / (C + G) is highly variable from one species to another - Associated with proteines (histones)  nucleosomic fibre (chromatine) - Denaturation & renaturation. 192 - Presents a structural and functional heterogeneity. - 3 main varieties: mRNA, rRNA and tRNA + snRNA - Synthesized by transcription of DNA - Each one has a special role in protein synthesis 193  Primary structure of RNA: Similar to DNA, but ose is the ribose & bases are 2 purines (A & G) & 2 pyrimidines (C & U). Secondary structure of RNA: - Single-chain: a single strand but often folded on itself (even matching rule that the DNA). - Association with specialised proteins  complexes of ribonucleoproteins (RNP) 194  Differents RNA: messenger RNA (mRNA): - Synthetized in the nucleus by transcription of DNA ds sequence (non coding strand) 1951`  - Carry the message of the G.I which will be translated by ribosomes into protein - Variable size and limited life (quickly produced and rapidly degraded - 2% of total RNA. Transfer RNA (tRNA): - Synthesized in the nucleus (nucleoplasm) - Transfer amino acids from the cytoplasm to the ribosome - 16% of total RNA - Structure: clover leaf. 196 197 Ribosomic RNA (rRNA): - Most abundant in the cell (82% of total RNA) - 4 varieties - Transcribed at the nucleolus (except 5S RNA) - Associated with proteins  preribosomal RNP - After maturation  cytosol to organize into ribosomes - Facilitate the binding of tRNA and mRNA on the ribosome during translation 198 Small RNA (snRNA or snRNP): - Associated with proteins - Involved in the maturation of mRNA, tRNA and rRNA. Ex; SNuRNP and SNoRNP - Some are essential in the synthesis of proteins in the cytosol. 199  Chapter III Plasma membrane (Plasmalemma)  Morphology, chemical composition, molecular architecture Specialization 200 PM & endomembranes consist of a set of active & dynamic molecules that provide: 1) Compartmentalization The continuous membranes enclose compartments: Plasma membrane enclose the content of entire cell Nuclear membrane enclose nucleus Cytoplasmic membranes enclose organelles Isolation: Specialized activities can proceed independently of outside and of one another 201 2) Exchange: Plasma membrane allows the transport of substances (energy, matter) to maintain the cell life Only desirable elements are exchanged between the compartments through pores and channels  selective exchange Responses to external signals: a signal propagates to stimulate or inhibit the activities inside the cell. 202  I. Morphology Like the walls of a house, PM protects the cell from external world Thin and fragile: 5 to 10 nm 10 000 Plasma membranes As thick as 203 203  Electron microscope/staining techniques Three-layered structure Trilaminar Appearance 2 dark layers (2.5 nm each) osmiophilic, separated by a clear sheet (3.5 nm) osmiophobe Asymmetric membrane (cell coat or glycocalyx) 204  II. Chemical composition The PM is a lipo-protein aggregates consisting of: - H2O - Lipids (40%), - Proteins (60%) - Carbohydrates (glycoproteins and glycolipids) The ratio (Prot / Lip) varies from one membrane to another: - 1.5 in PM - 1.1 in outer mitochondrial membrane - 2-3 in inner mitochondrial membrane 205 A. Membrane lipids AMPHIPHILIC contain: apolar hydrophobic part (hydrocarbon chains) a polar hydrophilic part (ex: substituted phosphoglycerol) Three types: 1. Phospholipids 2. Cholesterol 3. Glycolipids 206 1. Phospholipids The most abundant class of lipids of animal cells (55% of the lipid fraction) Two hydrophobic fatty acids of variable length (one of which contains one or more double bonds) + 1 phosphorylated polar head, which in turn binds to a polar substituent X (serine, choline, inositol......) The nature of the polar substituent X determines the nature of phosphoglyceride. PC, PS, PE, sphingomyeline, PI (in small quantities) 207 208 Amphiphilic lipids in aqueous solution form automatically a double layer membrane Air Water liposome 209 2. Cholesterol Very abundant in the plasma membrane of animal cells (30 to 50% of lipids). Absent from plants and bacteria PM. Type of steroid, consisting of a polycyclic polar head (OH) and an apolar tail. Integrated between the phospholipids, it occupies only a single layer of the lipid bilayer. OH Group at the interface 210 3. Glycolipids: 5 to 10% of membrane lipids Lipid molecules coupled to oligosaccharides oriented to the extracellular face Two types: - simple neutral glycolipids: cerebrosides - Complex glycolipids containing sialic acid (-): gangliosides. - Note that some gangliosides are receptors Ex: GM1 mono sialate is the receptor of cholera toxin. 211 B. Membrane proteins More diverse & more difficult to isolate than lipids. 50-70% (p + glycop). 30-50 times bigger than lipids amphiphilic: - 1 or many hydrophilic domains in contact with the cytosol or the extracellular medium; - 1 or many hydrophobic domains in contact with lipids. Enzymes, transporters, permeases, antigens, hormone receptors 212 Three categories: 1 - peripheral or extrinsic: 1/3 of PM proteins. Hydrophilic binding to the periphery (ext. / int.) by weak ionic bonds with mb components (hydrophilic regions of intrinsic proteins or polar head of membrane lipids). No contact with hydrophobic part Easily separated from the mb by salt solution Peripheral proteins on the cytoplasmic side are almost never glycosylated 213 214 2- Intrinsic or integral : Are much numerous Highly anchored in the mb. Provide important functions (Rc, enzymes, transporters..) 3 types: Monotopic: Rare, only attached to one side of the phospolipidbilayer. Ex: cytochrom b5. Bitopic: cross the phospolipidbilayer once and exposed separated domains on the extracellular and cytoplasmic faces. Ex: glycophorin & many receptors. Polytopic: many transmembrane segments. Ex: ABC transporter. Bitopic & polytopic are transmembrane proteins. 215  Most Integral proteins are transmembrane / amphiphilic (with α helices or β sheets) and the majority are glycosylated at extracellular side. 216 3- Lipid-anchored proteins: Outside of the lipid bi-layer (extracellular side). Covalently linked to membrane lipid by GPI (oligosaccharide). RARE Covalently anchored in the inner leaflet (at the cytosolic side) by a fatty acid (very long hydrocarbon chain): trimeric G proteins (if fatty acid is absent they become cytosolic). 217 C. Carbohydrates 5-10% and are located on the outer surface of the membrane. Two forms: - oligo or polysaccharids linked to proteins (glycoproteins or proteoglycans 93%) - oligo or polysaccharids linked to lipids (glycolipids 7%) Constitute "cell coat" or "glycocalyx“ (10 to 15 nm in thikness). 218  Carbohydrates bound to proteins or lipids. It provides a negative charge to the surface of many cell types Roles: - Protection to the cell from proteolytics enzymes - Enzymatic role - Permeability, endocytosis, intercellular adhesion - Cell – cell recognition 219 D. Characteristic of lipid bilayer 1. Assymetry: it depends on lipids, proteins & carbohaydrates composition Extracellular leaflet (exoplasmic) has more Phosphatidylcholine Sphingomyelin, & Glycolipids Equal for Cholesterol Intracellular leaflet (protoplasmic) has more Phosphatidylserine, Phosphatidylethanolamine, & Phosphatidylinositol 220  Disulfide bridges (S-S) are all found at the extracellular domains of proteins The membrane-cytoskeleton association is on the cytosolic face 2. Fluidity: proteins and lipids in the membrane are in permanent motion because there are no covalent bonds among them. = capacity to flow : depends on many factors: 221  Temperature: - At 37˚C, fluid state. Lipids are parallel & can move laterally - When the temperature decrease, lipids will transform into crystallized & frozen gel. The movement of lipids is greatly restricted Fluid Gel 222  The length of fatty acids chain and the degree of unsaturation: - Shorter chain  high fluidity: nb of interactions are less - More double bonds  high fluidity: chains stacking more difficult Example: plants in general are rich in unsaturated fatty acids in order to keep adequate fluidity when temperature drops at night and during winter The amount of cholesterol: Cholesterol acts as a bidirectional regulator of mbne fluidity - At high temperature, it decreases the fluidity - At low temperature, it intercalates between phospholipids promoting fluidity by preventing PL clustering 223 3. Movement of membrane constituents: Lipids : Shorter chain & more double bonds  speed lipids movement. a- diffusion: Movement between the two layers is almost impossible Without intervention of flipases lateral diffusion flip-flop rapid and slow and frequent rare 224  b- rotation : frequent & fast c- flexibility : depends on unsaturated fatty acids & cholesterol Proteins : may aggregate and move by: - lateral diffusion - rotation Generally lower - No flip-flop than lipids 225 Microdomains of the plasma membrane: Rafts: membrane differentiation: are clusters of sphingomyelin, glycolipids and cholesterol associated with membrane proteins (kinase-like signaling proteins). Lipid rafts play important roles in cell movement, endocytosis and cell signaling. Caveolae are a special type of lipids rafts containing caveolin protein. Important role in endocytosis of some viruses. 226 227 227 Mosaïc model 228  MEMBRANES TRANSPORTS 1- Selective permeabiliy: 229 2- Vesicular pathway: 230  II. Specialization A. Surface increasing 1- Microvilli : Extensions of PM observed on apical part of many cells (ex: enterocytes). Stable structures : - peripheral zone (PM) - central zone containing ~ 40 actin microfilaments of the same polarity (+ end toward PM), that are responsible for the microvilli mobility, grouped in bundles and connected together by fimbrin and villin These actin filaments are attached also to myosin filaments in the cytosol (terminal web) & are Linked to PM by myosin I and calmodulin. Have a highly developed cell-coat that facilitates their movement. Involved in absorption (e.g. enterocytes) or secretion. 231 233 234  Forms of micovilli Striated border : - straight μvill (same lengh & diameter) - Parallel and ordered - At the apical pole of enterocytes Brush border: - Identical to those of the striated border but are longer, looser and less regularly disposed 235 Brush border of enterocyte 236  stereocilia: - Immobile µvill - Without actin μfilaments - Irregular size and shape - Are sometimes anastomosed - Important in the secretion - In the male reproductive system (epididymis) 238 2- Basal folds: - Deep intracellular invaginations - Basal part of some epithelial cells (hydromineral exchanges) exchange that requires energy  need mitochondria. 239 B. Intercellular connections: junction & adhesion Organized & stable One cell binds to another structure, observed one, but by lack of at EM organizing structure 1. Intercellular junctions: Differentiation zone of PM Present in several cell types but are too abundant in the epithelia Interaction zone of the PM with the cytoskeleton 241  3 functional groups : a- Tight junctions (barrier) b- Intermediate junctions (mechanical) c- Gap junctions (exchange) 3 morphological groups : a- zonula type (full band) b- macula type (circular or oval task) c- fascia type (incomplete band) 242 a. Tight junctions or tight occludens or zonula occludens Located at the apical pole of cells such as enterocytes, seminiferous tubules). apical band Junctions has 5 leaflets Restrict the passage of mol. Contribute to cell shape determination Prevent lateral diffusion of proteins (polarisation) Formed by a network of anastomosis transmb proteins (occludin) linked to actin cytoskeleton by cytosolic proteins. 243 - Narrowed (plugged) intercellular space) - Several zipper-like structures 244 245 b. Intermediate junctions Also named belt desmosomes or zonula adherens It occurs in many tissues, especially in epithelia. Located at the apical part under tight junctions. Form a (belt) band that encircles the cell. 246  It Consists of: - Mb domain : transmembrane glycoproteins : cadherins whose adherence depends on Ca2+. - Cytoplasmic plaque composed of several proteins: attachment of the transmembrane glycoproteins (cadherins) with actin filaments of cytoskeletton by catenin. 247 248 c. Spot desmosome or Macula adherens : May occur everywhere between 2 neighboring cells Punctual junctions forming button-like attachment points It occurs abundantly in tissues submitted to mechanical pressure such as skin epithelia, uterus and cardiac muscle. Anchoring site of intermediate filaments (keratin if epithelial cell, desmin if heart cell, or other) 249  It Consists of: - Lamella formed by linkage of transmembrane glycoproteins (cadherin molecules) whose interation is Ca2+ dependent. - Cytoplasmic plaque: site of attachment of the IF with the cytosolic end of cadherin via two proteins; desmoplakin and plakooglobin. 250 251 1 Intercellular space 2 Cytoplasmic plate formed by desmoplakin 3 Desmoglein 4 Keratin filaments anchored into the cytoplasmic plate 252 253 d. Hemidesmosomes : macula type Connect basal surface of epithelia into the basal lamina. Constit of: - Integrins & other transmembrame proteins (adherence molecules). - Dense plaque of plectin against the inner surface of the PM and a bundle of intermediate filaments (keratin). 254 255 e. Synaptic junctions contact between axons of neurons and many cell types (muscle fibers, nerve cells). structure: 50 different members of cadherin allow the formation of action potential by release of neurotransmitters 256 f. GAP junctions (nexus) Exists in all cell types (except skeletal muscle cells and nerve cells). Pipeline-like structure CYTOP of cell A – CYTOP of cell B hydrophilic channel of 1.5 to 2 nm of diameter Allows easily the passage of polar 1 Open channel (1.5 nm) molecules < 2 nm. between adjacent cells 2 Intercellular space (2 - Structure: 6 subunits of polytopic 4 nm) proteins, connexins = 1 connexon 3 connexon composed of six sub-units of Not always opened: Regulated by pH and connexins Ca2+ Rotation of connexins (of a connexon) in a direction open the channel and rotation at 257 opposite direction close it 258 259 1 Tight junctions (zonula occludens) 2 Desmosomes (zonula adhaerens) 3 Desmosomes (macula adhaerens) 4 Gap junctions 260 2. Intercellular adhesion Cell adhesion molecules (CAM) : - CAM Ca2+ - dependent: cadherins and selectins. Selectins recognize and bind specific sugar motifs. Ex: intercation between leukocytes and endothelial cells of blood vessels wall at inflammation site allowing leukocyte infiltration to the damaged tissue. - CAM Ca2+ - independent : Immunoglobulins family (immune functions). Ex: intercation between lymphocytes and macrophages. Cell-matrix adhesion molecules (SAM): - integrins (Ca2+ dependent) - laminins and fibronectin They contribute to epithelium adhesion to the basement mbne 261