Histology of the Human Cell 24 PDF

MAIN TITLE: Histology SUBTITLE: The Ultrastructure of Cell Online Lecture Materials LECTURER: Prof. Yeşim ULUTAŞ UĞUR M.D PLASMA MEMBRANE (CELL MEMBRANE)...

MAIN TITLE: Histology SUBTITLE: The Ultrastructure of Cell Online Lecture Materials LECTURER: Prof. Yeşim ULUTAŞ UĞUR M.D PLASMA MEMBRANE (CELL MEMBRANE) Essential for viability of the cell A dynamic structure Organized as bilayered lipid Contains two electron-dense (dark) & one electron-lucent (light) layers Has 8-10 nanometers thickness Contains embedded «integral membrane proteins» Has attached «peripheral membrane proteins» Defined as «modified fluid-mosaic model» PLASMA MEMBRANE PLASMA MEMBRANE (CELL MEMBRANE) Cholesterol Protein Phospholipid Glycoprotein (at the surface forms glycocalyx) Glycolipid (at the surface forms glycocalyx) Has hydrofobic (central) & hydrophilic parts PLASMA MEMBRANE (CELL MEMBRANE) Glycocalyx acts as receptor Lipid rafts are areas where cholesterol & glycosphingolipids are found at high concentrations Lipid rafts provide the movement of proteins within plasma membrane Lipid rafts provide intercellular communication (signaling) INTEGRAL MEMBRANE PROTEIN TYPES Receptor Linker Pump Canal (channel) Enzyme Constitutive protein PLASMA MEMBRANE  INTEGRAL MEMBRANE PROTEINS Receptor Linker Endocytosis Cytoskeleton-extracellular Immune reactions matrix interactions Hormonal stimulation  INTEGRAL MEMBRANE PROTEINS Pump Canal (channel) Active ion transport Passive diffusion Transport of macromolecule Water transport precursors Transport of small molecules Transport between cells INTEGRAL MEMBRANE PROTEINS Enzyme Constitutive protein ATPase Junctional units Dipeptidase Disaccaridase TRANSPORT TYPES AT THE PLASMA MEMBRANE ❖Simple diffusion ❖Structures constructed by proteins Voltage-gated channels Ligand-gated channels Mechanically gated channels ❖Mechanisms functioning through mobile molecules Passive transport (glucose) Active transport (ion pumps)  TRANSPORT TYPES AT THE PLASMA MEMBRANE ❖ENDOCYTOSIS (taking into cytoplasm) Pinocytosis (water & small molecules) Phagocytosis (large molecules & structures) Receptor-mediated (by binding to the specific ligand) ❖EXOCYTOSIS (giving out of cytoplasm) Constitutive (works continuously) Regulated (works only when needed) ENDOCYTOSIS AT THE PLASMA MEMBRANE Pinocytosis & phagocytosis are clathrin-independent Receptor-mediated endocytosis is clathrin-dependent A coated vesicle is formed Receptor interacts with clathrin via ADAPTIN DYNAMIN is the enzyme of the act  EXOCYTOSIS AT THE PLASMA MEMBRANE Sorting & packing occur within Golgi apparatus Cargo is coated by a «coatomer» Targeting is provided COP I or COP II TRANSCYTOSIS TRANSCYTOSIS vesicle  ENDOSOME ❖Early endosome Constructed by fusion of plasma membrane-originated vesicles Located near the plasma membrane Sorts internalized proteins (some are returned back to membrane) Inner environment is not acidic yet ❖Late endosome Inner environment is acidic Located near Golgi apparatus & nucleus  LYSOSOME Originates from endosomal structures Contains enzymes that provide degrading or destroying Lysosome-specific membrane proteins & lysosomal enzymes are added to the endosomal structure  LYSOSOME Endosomes & lysosome have mannose-6-phosphate receptors Mannose-6-phosphate is added to the cargo before leaving Golgi apparatus  LYSOSOMAL MEMBRANE Cholesterol, lysobisphosphatidic acid Proton (H+) pumps Transport proteins LIMP (lysosomal integral membrane protein) LAMP (lysosome-associated membrane protein) LGP (lysosomal membrane glycoprotein) Primary lysosome Secondary lysosome  PROTEASOME Ubiquitin is added to the cargo to target the proteasome Contains ATP-dependent protease complexes Degrades abnormal proteins Recycles short-lived normal regulatory proteins for reuse PROTEASOME  PEROXYSOME (microbody) Provides detoxification (hydrogen peroxide is toxic) Contains oxidative enzymes (peroxidases) Surrounded by membrane Provides fatty acid degradation  ENDOPLASMIC RETICULUM Granular endoplasmic reticulum (GER) Smooth endoplasmic reticulum (SER) Protein synthesis occurs in granular endoplasmic reticulum & ribosomes GER-containing cytoplasm is defined as ergacytoplasm Organized as membrane-limited continuous stacks Stacks have spaces called as cisterna GRANULAR ENDOPLASMIC RETICULUM Cytoplasmic surfaces of cisternae contain ribosomes Ribosomes are protein synthesizing factories A single ribosome has small & large subunits Each subunit has ribosomal RNA (rRNA) GRANULAR ENDOPLASMIC RETICULUM A group of ribosomes is defined as polysome Ribosomes are attached to messenger RNA (mRNA) threads GER is continuous with the outer leaflet of nuclear envelope Ribosomes can also be found freely within the cytoplasm PROTEIN SYNTHESIS (Transcription & Translation) Transcription occurs within nucleus Genetic code is organized as codons (as base triplets) Genetic code is copied from DNA to form a transcript Pre-mRNA is formed initially Pre-mRNA is exposed to post-transcriptional modifications like intron excision mRNA is formed & leaves the nucleus PROTEIN SYNTHESIS (Transcription & Translation) Translation occurs within cytoplasm Ribosomes read the message coded by mRNA mRNA contains anti-codon A single mRNA chain binds to a lot of ribosomes A single mRNA is translated Polypeptides are formed PROTEIN SYNTHESIS (Transcription & Translation) Involved aminoacid is carried towards its mRNA by its specific tRNA Aminoacid has a signal peptide that indicates its target Signal peptide binds to signal recognition particle (SRP) SRP links to docking protein PROTEIN SYNTHESIS (Transcription & Translation) SRP-docking protein complex interacts with translocator Signal peptide is cropped by signal peptidase Main part is transferred into GER cisterna Ribosome returns back to cytoplasm (Boumphreyfr’in çizimi) t POST-TRANSLATIONAL MODIFICATION Within GER cisterna modifications occur through enzymes Like folding by chaperons, glycosylations After modifications products move towards Golgi apparatus TRANSPORT BETWEEN GER & GOLGI APPARATUS Transport between GER & Golgi apparatus is provided by coatomers Anterograde transport is from GER towards Golgi apparatus COP II works for anterograde transport Retrograde transport is from Golgi apparatus backwards to GER COP I works for retrograde transport TRANSPORT BETWEEN GER & GOLGI APPARATUS COP I carries abnormal protein back before it moves further COP I also works between Golgi cisternae again in a retrograde fashion Cargo dissociates from its coatomer when it reaches its target  FREE RIBOSOMES Some functional cytoplasmic elements are produced by free ribosomes residing within cytoplasmic matrix SMOOTH ENDOPLASMIC RETICULUM SMOOTH ENDOPLASMIC RETICULUM LACKS ribosomes Its stacks are tube-shaped Prominent in steroid-synthesizing cells, involved in lipid & glycogen metabolism Functions in detoxification Neutralizes toxic substances by conjugation Named as sarcoplasmic reticulum in skeletal & cardiac muscles Stores calcium Regulates intracytoplasmic calcium concentration  GOLGI APPARATUS Organized as membranous stacks A polarized organelle GER-facing side is called as cis-Golgi network (CGN) Cargo-releasing side is called as trans-Golgi network (TGN) Between them there is the medial-Golgi network Transport vesicles transfer cargo between cisternae Well-developed in secretory cells  GOLGI APPARATUS Functions are sorting & packing: Proteins to be secreted to the extracellular environment Proteins to be added to the structure of plasma membrane Proteins to be carried to late endosomes & lysosomes Provides the final post-translational modifications of proteins Phosphate & sulphate groups are added to the final cargo MITOCHONDRION  MITOCHONDRION Produces energy (ATP) Can be stained & displayed by Janus green (vital dye) Divides & proliferates Its division cycle is not synchronized with the cell cycle Changes location & shape Acidophilic staining-pattern Erythrocytes lack mitochondria  EVOLUTION OF MITOCHONDRION Long ago it was an aerobic bacteria & evoluted in human cell Owes its own genome Produces its own ribosomes Produces some of its constitutive proteins by itself Has a closed-type circular DNA Owes its own rRNA & tRNA to provide the translation of mRNA Via its DNA produces 13 self-enzymes Other mitochondrial proteins are produced by free ribosomes  MITOCHONDRIAL MEMBRANES Has outer & inner membranes Space between these two membranes is defined as intermembrane space The medium enclosed by the inner membrane is named as matrix Inner membrane surrounds the matrix  MITOCHONDRIAL MEMBRANES There is a transport traffic between mitochondrial membranes This transport needs energy & CHAPERON proteins Transporters: TOM complex Translocase of outer mitochondrial membrane TIM complex Translocase of inner mitochondrial membrane OUTER MITOCHONDRIAL MEMBRANE It is a smooth membrane Contains canals (channels) named as porins Porins are open to large uncharged molecules (these molecules can not pass inner membrane freely) Contains the receptors for proteins & polypeptides that are to be carried into the intermembrane space Has enzymes INNER MITOCHONDRIAL MEMBRANE Thinner than outer membrane Has folds defined as cristae Cristae extend towards matrix Cristae increase surface area Cristae are tubular-shaped in steroid synthesizing cells Inner membrane is impermeable to ions Cardiolipin (a phosfolipid) provides this function INNER MITOCHONDRIAL MEMBRANE PROTEINS «Respiratory electron transport chain» extends towards the matrix Contains tennis racket-shaped structures defined as elementary particles Elementary particles contain enzymes Elementary particles provide ATP synthesis via oxidative phosphorylation INTERMEMBRANE SPACE OF MITOCHONDRION ATP produced at the inner membrane is used at the intermembrane space Contains enzymes: Cytochrome c (initiates apoptosis) Kinases  MITOCHONDRIAL MATRIX Matrix granules: Calcium stores Contains enzymes of citric acid cycle (Krebs) & for beta oxidation of fatty acids Matrix also contains mitochondrial DNA, tRNA & ribosomes Matrix reactions: CO2 & NADH is produced FUNCTIONAL CONFIGURATIONS OF MITOCHONDRION Orthodox configuration: Cristae are prominent Matrix is enlarged Indicates to low level of oxidative phosphorylation Condense configuration: Cristae are NOT prominent Matrix area is limited & condense Intermembrane space is wide Indicates to high level of oxidative phosphorylation  MICROTUBULE Forms cell shape & cytoskeleton Responsible from intracellular transport & cellular movement- migration Present within cell processes-arms Provides the movement of cilium & flagellum (example: in spermium) Provides attachment & movement of chromosomes via the mitotic or meiotic spindle during cell division  MICROTUBULE A hollow tube made up of proteins A dynamic structure which polymerizes when needed then depolymerizes when the need is over Cell vesicles move & are transported via them Originates from “microtubule-organizing center (MTOC)” MTOC is located near the nucleus  MICROTUBULE A polymer made up of alpha & beta tubulin proteins 13 globular dimeric tubulins are circularly arranged “Microtubule organizing center (MTOC)” contains gamma tubulin rings Alpha & beta tubulin proteins originate from gamma tubulin rings  MICROTUBULE A polarized structure Has negative (non-growing) & positive (elongating) poles Negative pole is at the “microtubule organizing center (MTOC)” side When the cell does not need any, waits as free tubulin dimers within the cytoplasm Microtubule-associated proteins (MAPs) Provide microtubule formation & attachment to specific structures In cilium (respiratory system) & flagellum (spermium) MAPs inhibit microtubule depolymerization  MICROTUBULE Acts as a road Movement on the road is provided by “molecular motor proteins” Molecular motor protein attaches to cargo & leads a track for its transfer towards the target Molecular motor proteins are: “Kinesin” & “Dynein” Kinesin carries towards the positive end Dynein carries towards the negative end  MICROFILAMENT Actin is the microfilament Actin has globular (ball-like) & filamentous (thread-like) forms When there is no need it is in globular form within cytoplasm When in need it polymerizes and changes into its filamentous form  MICROFILAMENT Filamentous actin is a polarized structure Rapidly-growing end is called as positive end Slow-growing end is called as negative end MICROFILAMENT-ASSOCIATED PROTEINS Actin-binding proteins Actin-bundling proteins Actin-severing proteins Actin-capping proteins Actin cross-linking proteins Actin motor proteins  MICROFILAMENT Mostly located near plasma membrane Form a terminal web immediately beneath apical cell surface to construct & stabilize cell shape Intracytoplasmic attachment point of junctional units Via polymerization provides movement of the cell  INTERMEDIATE FILAMENT Acts as cytoskeleton NOT polarized SPECIFIC to tissue Provides linkage between cytoplasm & extracellular environment  INTERMEDIATE FILAMENT TYPES Type 1 & Type 2: Acidic & basic cytokeratins are found in epithelial cells Type 3: Vimentin is found in fibroblasts Desmin is found in myocytes Type 4: Neurofilaments Type 5: Lamins Type 6: Beaded-filaments INTERMEDIATE FILAMENT-ASSOCIATED PROTEINS In the links between neighboring cells, cells & extracellular matrix In desmosomes  CENTRIOLE Found as two short sticks arranged at an angle of 90 degrees to each other Made up of 9 microtubule triplets  CENTRIOLE Centriole pair is located within “pericentriolar material” Pericentriolar material & centrioles are together called as “CENTROSOME” or “microtubule organizing center (MTOC)” Centrioles give rise to basal bodies which are sources of cilia & flagella Centrioles form mitotic or meiotic spindles during cell division  CENTRIOLE Each microtubule within a centriole is made up of 13 globular dimeric tubulins Each microtubule triplet have 3 types of microtubules named as A, B&C Neighboring microtubules share common parts «A» microtubule is a complete ring so contains 13 globular dimeric tubulins But «B» & «C» microtubules are incomplete & half moon-shaped, they share some part of their neighbors’ rings  CENTRIOLES BASAL BODIES & CILIOGENESIS Cilium formation is called as «ciliogenesis» Basal bodies are involved in ciliogenesis Kinocilium is the movable process of the cell (Stereocilium is the non-moveable process of the cell & does not contain axoneme)  CENTRIOLES BASAL BODIES & CILIOGENESIS Cilium has two central separated & 9 peripheral conjoined paired microtubules This structure is called as “axoneme» Axoneme originates from the A & B microtubules of the basal body BASAL BODY AXONEME  NUCLEAR ENVELOPE Separates cytoplasm from the nucleoplasm Composed of two membranes Between outer & inner membranes “perinuclear cisternal space” is located This space is in continuation with GER cisternae It is a selective barrier  NUCLEAR ENVELOPE Where inner & outer membranes meet there are «nuclear pores» Active transport of cellular materials is provided via these pores (holes) RNA & proteins are transported between nucleoplasm & cytoplasm via these pores  OUTER NUCLEAR MEMBRANE Structure is similar to endoplasmic reticulum membrane Has ribosomal docking proteins at the cytoplasmic face Polyribosomes are attached to these dockers  INNER NUCLEAR MEMBRANE Nucleoplasmic face is supported by intermediate filament network This network is called as “nuclear fibrous lamina” Lamina contains “nuclear lamins” & “lamin-associated proteins” These proteins attach to chromosomes Involved in DNA replication & transcription During cell division nuclear lamina is disrupted but reformed after the event Inner nuclear membrane owes “lamin receptors”  NUCLEAR PORE “ Nuclear pore complex (NPC)” is a cylinder surrounded by 8 proteins These proteins are of different types & called as “nucleoporins” Ribosomal subunits are produced within nucleolus Ribosomal subunits pass through nuclear pores while transferring into the cytoplasm  NUCLEAR PORE Histons & lamin like nuclear proteins are produced within cytoplasm & transferred to nucleus through nuclear pores Large molecules can only be allowed through nuclear pores if they carry “nuclear localization signal” Molecules carrying this signal link to the cytoplasmic soluble receptor “importin” to gain access to nuclear pores  NUCLEAR PORE Transport from nucleus to cytoplasm is provided by “nuclear export sequence (NES)” & “exportin” RNA, ribosomal subunits are carried to the cytoplasm via this way  NUCLEOPLASM «Nucleoplasm» is the material surrounded by nuclear envelope excluding chromatin & nucleolus  NUCLEOLUS NOT surrounded by a membrane It is the area where transcripting rRNA genes are found It is the site where ribosome production is initiated Ribosomal RNA (rRNA) synthesis takes place Ribosomal subunits are produced A single nucleus may contain more than one nucleolus  NUCLEOLUS Parts of nucleolus: Fibrillar center: The DNA containing rRNA genes Fibrillar material (pars fibrosa): Ribosomal genes at transcription Granular material (pars granulosa): The site where ribosomal subunits are formed  NUCLEOLUS Nucleolar content is totally called as “nucleolonema” Nucleolus is also the site where cell cycle is controlled  INCLUSION Remnant of metabolic activity Pigment granules (SURROUNDED by PLASMA MEMBRANE) Lipofuscin pigment (bacteria, particles, dead cells, defunct organelles) Lipid droplets (surrounded by vimentin) Glycogen granules Hemosiderin (iron-store complex) Crystalline inclusions (in some testicular cells, viral proteins)  CYTOPLASMIC MATRIX Electrolites Metabolites RNA Proteins  USED REFERENCES Histology A Text and Atlas Wheater’s Functional Histology Ross, Pawlina Young, Woodford, O’Dowd Textbook of Histology Essential Histology Gartner Cormack Junquiera’s Basic Histology: Human Histology Text and Atlas Stevens, Lowe Mescher Netter’s Essential Histology Ovalle, Nahirney THANKS FOR 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