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membrane lipid raftsspecialized membrane microdomains containing receptors that signal inside the cell for specific functionssimple diffusionmovement of a solute from an area of high concentration to an area of low concentration without energy requirementsfacilitated diffusionmovement of molecules across cell membrane through transport proteins. Does not require energy and movement proceeds from high to low concentration.main difference between passive and active transportPassive transport does not require energy, while active transport requires energyactive transportmovement of molecules against concentration gradient which requires energy or ATPTransport of large molecules across the cell membranemovement is mediated by vesicles. endocytosis transports substances from external environment to cytosol, while exocytosis exports substances outside the cytosol.intracellular membranesendoplasmic reticulum, Golgi apparatus, lysosomes and vesicles, nuclear envelopepercentage of endoplasmic reticulum among intracellular membranes50%Structural difference between rough and smooth endoplasmic reticulumRough endoplasmic reticulum has ribosomes bound to its outer layerfunction of ribosomesprotein synthesisdirection of products of free ribosomesnucleus, mitochondria, cytoskeleton, peroxisomes, inner plasma membranedirection of products of RER-bound ribosomesexport proteins: outer plasma membrane, lysosomes, extracellular environmenthow do proteins move from the ribosomes to the ERfirst 5-30 amino acids encode a signal peptide, which binds to a signal recognition particle. the signal recognition particle binds to a receptor of the ER membrane.Functions of the RERpost translational modifications of proteins, protein folding, assembling of quaternary structures, beginning of protein glycosilation, hydroxilation of lysine and proline residuesFunctions of the SERSynthesis of steroids, lipids and lipidic components of the cell membranes, storage of ions, detoxification of the cell, glycogen metabolismStructure of the Golgi apparatusMembrane bound sacs. Sacs are disc-like and often curved.Functions of the Golgi ApparatusModification of proteins by glycosylation, proteolysis or phosphorylation, synthesis of glycosaminoglycans, sorting and delivery of proteins to specific locations through vesicles, selection of lysosomal enzymesSignaling of proteins directed to the ERKDEL signal, which is recognized through a KDEL-receptorSignaling of proteins directed to lysosomesProteins are marked by 6-phosphate mannoseconstitutive secretion of proteins in the EC environmentvesicles contain coating proteins (COPs) and are not regulated by a specific stimulusRegulated secretion of proteins in the EC environmentvesicles are coated by chlatrin-like proteins, and secretion is mediated by specific signals such as neurotransmitters, hormones or enzymestypes of endocytosisreceptor-mediated endocytosis, phagocytosis, pinocytosis, autophagyexocytosisProcess of transport of large molecules outside the plasma membrane in which vesicles originate intracellularly and fuse with the plasma membrane, releasing their content. Can be constitutive or regulated.GemmationProcess of transport of large molecules outside the cell in which the vesicle originates from the plasma membrane. substances secreted to the EC environment are enclosed into a vesicle.Advantages of vesicle coatingCoating favours bending of membrane, allows selection of components that are transported, impacts direction and destinationCOPIIMove from the ER to GolgiCOPIMove from Golgi to ERChlatrin coatingMove substances from the Golgi to the plasma membrane or endosomes/lysosomesv-SNARE and t-SNARETransmembrane proteins located on the vesicle and on the target membrane respectively, which interact for the correct destination of a vesicleChlatrin-mediated endocytosischlatrin molecules aggregate and form a basket-shaped netowrk on the cytoplasmic side of PM, dynamin molecules bind GTP and the aggregate and help with detachment of the vesicle.PinocytosisNon-specific introduction of small liquid droplets in the extracellular fluidWhat is phagocytosis and who performs it?Engulfing of solid matter, organic or inorganic, inside the plasma membrane. It is performed by phagocytes, which include macrophages, neutrophils, granulocytes etc.Phases of phagocytosisRecognition and absorption, internalization inside the plasma membrane, digestion inside lysosomesLysosomesMembrane-bound organelles that contain digestive enzymesWhere are lysosomal enzymes synthesized, and how are they recognizedLysosomal enzymes are assembled in the RER aand are marked by 6-phosphateWhat types of cells contain abundant lysosomes?Cells that perform intense phagocytosis have abundant lysosomes, including macrophages, granulocytes, immune cellsHow is the acidic environment of the lysosomes maintained?Lysosomes have a H+ pump on their plasma membrane which regulates pH for the efficient functioning of digestive enzymes.Specialized lysosomes in the skinMelanocytes contain granules, melanosomes. they are modified lysosomes which store melanin.Lysosomal storage diseasesRare genetic diseases caused by defects of lytic enzymes. They consist in the abnormal accumulation of substances inside lysosomes and are abundant in children. They may cause developmental delays, organ defects, movement disorders, dementia and early death.Peroxisomes: structure and functionSingle membrane-bound organelles containing enzymes involved in metabolic activities. They have variable shape and size and contain high amounts of catalase: in fact they are involved in amino acid and fatty acid oxidation, which produce hydrogen peroxide, a toxic substance that is degraded by catalase. They are involved in detoxification processes of the cell and are abundant in hepatocytes and renal cells.Cells of the nervous tissue with high concentration of peroxisomesOligodendrocytesFunction of mitochondriaTHEY ARE THE POWERHOUSE OF THE CELL! They produce ATP for functional and metabolic activity of the cell, and perform cellular respiration. ATP is obtained by oxidation of pyruvate, which derives from glycolysis of glucose.Structure of mitochondriaThey are double-membrane bound organelles with a plastic shape. The outer membrane is smooth, and rich in lipids such as phosphatidylcholine, while the inner membrane is folded in lamellar or tubular structures called cristae, and contain enzymes and transmembrane proteins involved in ATP synthesis. The space between membranes is called intermembranous space, and contains cytochrome C, which is involved in the electron transport chainbiochemical difference between inner mitochondrial membrane and other membranous componentsThe inner mitochondrial membrane contains cardiolipin instead of cholesterol: this feature makes it more similar to bacterial cell membranes, and adds evidence to the endosymbiotic theory.regular and condensed mitochondriaregular mitochondria have abundant matrix and limited intermembrane space, while condensed mitochondria have abundant intermembrane space due to accumulation of H+ ions, which signals high oxidative phosphorylationaverage number of mitochondria in a cell1000-2000average number of mitochondria in an oocyteup to 30kexamples of cell with abundant mitochondriaskeletal muscle fibers, cardiac muscle fibers, kidney tubular cells, spermatozoa tails, ciliated cells, presynaptic terminal of neuronssemi-autonomous features of mitochondriamitochondria have their own genome, DNApol, RNApol and ribosomes, and replicate through segmentation. However, many mitochondrial proteins are synthesized in the cell nucleus and imported into mitochondria.Embryologic origin of mitochondriaAll mitochondria in a cell are of maternal inheritance: paternal mitochondria are in fact phagocyted or dispersed during the first cycles of replication of the zygote. This particular feature allows limited recombination and is important for evolutionary studies.Autogenous Hypothesis for mitochondriaThe autogenous hypothesis states that mitochondria segregated from part of the cell genome and were enveloped by plasma membrane.Endosymbiotic hypothesis for mitochondriaThe endosymbiotic hypothesis states that mitochondria were originally prokaryotic cells, which developed a symbiotic relationship with a eukaryotic cell. This would explain the nature of the double membrane, and the different composition of the inner membrane with respect to the other membranous structures.Functions of mitochondriaProduction of ATP by cellular respiration, lipid and phospholipid metabolism, synthesis of steroid hormones, accumulation of cations, heat production, apoptosis.Functions of the cytoskeletonProvides supporting strucure to cell components, determines organelle position, regulates vesicle trafficking, provides mechanical links against tension, allows chromosomal separation during mitosis/cytokinesis, provides mechanism for muscle contraction, determines cell motilityMicrofilamentsActin filaments with a diameter of 7nm, located around the cell close to the plasma membrane. They can be stationary or dynamic.Intermediate filamentsFilamentous proteins of variable nature (depends on cell differentiation), with a diameter of 10nm, which provide mechanical strength to cells. They are located all over the cytoplasm and are only stationary.MicrotubulesFibers of the cytoskeleton with a diameter of 25nm, which originate from the internal region of the cell and spread towards the periphery. Can be both stationary or dynamic.Structure of microfilamentsF-actin (actin filaments) organized in G-actin (globular actin) in a double helix structure.Functions of microfilamentsProvide cell scaffold and allow cell movement, are responsile for anchoring and movement of membrane proteins, they form the structural core of microvilli, are responsible for lamellipodia (locomotion), and for the extension of cell protrusions (filopodia).Actin mediated motilityActin filaments in motile cells are responsible for movement in space: a ligand-receptor binding on the membrane causes formation of a lamellipodium (cytoplasmic extension), which forms an adhesion plaque between cell and substrate. Then, the cell translocates towards lamellipodium and adhesion plaque, and retrograde adhesion is detached.Cell migrationCell motility is triggered by chemotactic gradients of substances binding to receptors of the plasma membrane.Structure of intermediate filamentssingle proteins assemble in dimers, which assemble in tetramers. Several tetramers assemble to form filaments.intermediate filaments in epithelial cellsKeratinintermediate filaments in connective tissueVimentinintermediate filaments in muscle tissueDesminintermediate filaments in neural tissueGlial Fibrillary Acidic Proteins (GFAP)intermediate filaments in cell nucleusLaminImportance of intermediate filaments in cancer diagnosisThey are used to determine the origin of a cancer, because every tissue has intermediate filaments specificity. By determining the IF composing cancer cells, it is possible to determine the origin of the tumor.Structure of microtubulesRigid and hollow tubes made of alpha and beta tubulin dimers, arranged in 13 protofilaments. Protofilaments are arranged circularly around the central lumen.functions of microtubulesScaffold for cell organelles, maintenance of cell shape, composition of the mitotic spindle and segregation of chromosomes, movement of substances among cell compartments.microtubule organizing center (MTOC)Also called centrosome, is the location of origin of microtubules near the nucleus, from which microtubules extend towards the periphery. It is composed of two orthogonal centrioles, each one made of 9 sets of triplets of microtubules. It plays a role in the organization of the mitotic spindle for segregation of chromosomes during cell division, mitosis or meiosis.Polarization of microtubulesMinus end is located towards the MTOC, while plus end is located towards periphery. Polarization is important for molecular movement: kinesin carries substances from the minus to the plus end of microtubules, while dynein carries substances from plus to minus end of microtubules.Microtubule mediated motilityMicrotubules constitute the core of cilia, which are apical specializations 5-10 micron long. They are important for movement o substances along the lumen of hollow organs and form the tail of spermatozoa (flagellum).Microtubules in cancer therapyMicrotubules are the target of several anti-cancer drugs, which inhibit the polymerization of the mitotic spindle and prevent cell proliferation. These drugs have very low specificity, which means that they inhibiti proliferation of all cells, even healthy ones.Functions of cell nucleusContains the genetic information encoded in the DNA, directs protein synthesis in the cytoplasm by synthesizing mRNAsyncitiumMultinucleated cell formed by the fusion of originally separated cellsStructure of the nuclear membrane/nuclear envelopeDouble bilayer membrane with nuclear pores. The outer membrane is in continuity with the ER, while the inner membrane contains proteins interacting with the nuclear lamina.heterochromatincondensed DNA, functionally inactiveEuchromatindisperse DNA, functionally activeNuclear laminaArray of intermediate filaments of lamin, located between the nuclear envelope (membrane) which confirs shape and structural link between DNA and nuclear envelopeImportance of nuclear lamina in cell reproductionThe nuclear lamina is disaggregated during prophase by phosphorylation of lamin, and reaggregated by telophase by dephosphorylation.number of nuclear pores in a somatic cell10-20 pores/square micronnumber of nuclear pores in oocytes40-50 pores/square micronNuclear pore complexBasket shaped openings in the nuclear envelope which mediate movement of substances in and out of the nucleus. They are constituted by cytoplasmic, nuclear and distal rings which anchor proteins, cytosol fibrils which capture substrates and receptor for mediation of substances.Nuclear trafficking from cytoplasm to nucleustranscription factors, proteins for chromosomal replicationNuclear trafficking from nucleus to cytoplasmProteins for ribosomal maturation, protein synthesis material, RNANucleolusNon-membranous portion of the nucleus, site of ribosomal synthesis and assembly. Granular appearance, surrounded by nucleolus associated chromatin. Disappears during mitosis.Cell cyclePeriod between two cell divisions, composed of 4 phases: G1, in which there is protein synthesis and organelle doubling, S when there is duplication of DNA, G2, in which there is synthesis of cytoplasmic components and assembly of the mitotic spindle, Mitosistiming of G18 hours or moretiming of S phase7-10 hourstiming of G22-5 hourstiming of M phase1-2 hoursLabile Cells + Examplescells in continuous renewal which never escape the cell cycle. Labile cells are epithelial linings of mucosaeStable cells + ExamplesCells which can replicate in response to request, with quiscent and reversible G0. Stable cells are glandular tissues.Static Cells + ExamplesStatic cells have no proliferation potential and remain in G0 permanent phase. Static cells are neurons, cardiomyocytes, skeletal muscle cellsApoptosisprogrammed cell death by fragmentation of nuclear and cytoplasmic components, which are eliminated by phagocytosis. This process does not cause inflammation.NecrosisCell death by injury, which leads to swelling and cell lysis. This process leads to inflammation.Changes occurring in cells before apoptosisDecreased cell dimensions, DNA fragmentation, translocation of phosphatidyl-serine from cytoplasmic to extracellular side of the plasma membrane, depolarization of mitochondrial membrane potential, release of cytochrome C from the intermembrane space of mitochondria, activation of cytoplasmic enzymes caspases that digest intracellular substances.AutophagyProcess that eliminates aged and damaged organelles/molecules for renewal and repair, elimination of pathogens and protection against DNA damage.Process of autophagyIsolation of a part of membrane and formation of a phagophore vesicle, which engulfs cytoplasmic components, then the autophagosome (closed vesicle) fuses with lysosome for degradation of content, and finally autolysosome.
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