The cell
Abstract
The cell is the basic structural and functional unit of living organisms. While unicellular organisms (e.g., bacteria, protozoa) consist of a single cell capable of sustaining life, multicellular organisms (e.g., animals, land plants) consist of numerous highly specialized and diverse cells organized into various types of tissue. Cells are surrounded by a membrane composed of a lipid bilayer with embedded proteins. Depending on their cell structure, organisms are classified prokaryotes or eukaryotes. Prokaryotes, which encompass the domains of the Bacteria and the Archaea, are unicellular organisms that lack membrane-bound organelles such as a nucleus and mitochondria (see bacteria overview). Eukaryotes are unicellular and multicellular organisms, whose cell or cells contain various specialized, membrane-bound organelles such as a nucleus and mitochondria.
Cell types
Cell types are classified as either prokaryotic or eukaryotic. Prokaryotes are unicellular organisms that encompass the domains of Bacteria and Archaea. They consist of a single cytoplasm-filled compartment enclosed by a cell membrane. Eukaryotes contain a nucleus and other membrane-bound cell organelles. Eukaryotes encompass all multicellular organisms as well as some unicellular ones (protozoa). Eukaryotic cells are larger (100–10,000-fold) than prokaryotic cells and possess a significantly higher degree of complexity in terms of structure.
Eukaryotes | Prokaryotes | |
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Nucleus |
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Location of DNA |
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DNA storage form |
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Amount of noncoding DNA |
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External boundaries |
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Compartmentalization |
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Locomotive structures (flagellum) |
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Prokaryotic cells do not have a nucleus!
Cell membrane
Both prokaryotes and eukaryotes have cell membranes. The cell membrane provides a boundary to the cell interior and is an essential component of living systems. Eukaryotic cells also have intracellular membranes that envelop individual organelles and enable specialized processes to occur within in separation from cytoplasmic processes. Most prokaryotic and plant cells furthermore possess a cell wall, which envelops the cell membrane and protects cells from external influences.
Cell membrane structure
The cell membrane is composed of a lipid bilayer with embedded or attached membrane proteins. The synthesis of membrane components occurs in the smooth endoplasmic reticulum (sER).
Lipid bilayer
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Structure: The fundamental building blocks are amphiphilic lipids such as phospholipids or sphingolipids, which possess a polar head (e.g., phosphate, sphingosine) and hydrophobic tails (fatty acids).
- Distribution of nonpolar and polar groups: In an aqueous solution, the nonpolar hydrocarbon tails face inward, while the polar heads form a boundary to water in both directions. As a result, stable lipid bilayers develop, forming a spherical entity (e.g., cells or vesicles).
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Distribution of membrane lipids: The different types of lipids are distributed asymmetrically between the two leaflets of the membrane.
- Outer lipid layer: rich in phosphatidylcholine and sphingomyelin
- Inner lipid layer: rich in phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol
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Characteristics
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Permeability
- Almost impermeable to polar molecules
- Highly permeable to nonpolar molecules and water
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Fluidity: The fluidity of the membrane lipid bilayer changes depending on the composition of the lipid bilayer and temperature of the environment.
- Unsaturated fatty acids increase membrane fluidity.
- Cholesterol stabilizes the membrane.
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Diffusion: The fluidity of the lipid bilayer allows for movement of individual molecules within the membrane.
- Lateral (parallel) diffusion: Individual lipid molecules diffuse freely within the lipid bilayer.
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Transverse diffusion : very slow, requires enzymatic support by flippases, floppases, or scramblases (phospholipid translocators)
- Flippases: move phospholipids from the outer to the inner surface
- Floppases: move phospholipids from the inner to the outer surface
- Scramblases: move phospholipids in both directions
- Facilitated diffusion: diffusion of molecules across the cell membrane via carrier proteins, channel proteins, or ions (e.g., glucose and fructose transport into cells via GLUT transporters)
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Permeability
Membrane proteins
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Definition
- Proteins that are embedded in the lipid bilayer of membranes
- Usually glycoproteins
- Membrane protein content in the lipid bilayer: 20–80%
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Types of membrane proteins
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Integral membrane proteins
- Strongly bind to the lipid bilayer
- Partially penetrate into the membrane
- Transmembrane proteins: completely penetrate the lipid double layer (e.g., Na+/K+-ATPase)
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Peripheral membrane proteins
- Poor binding to the lipid bilayer
- Usually bind via electrostatic affinity or hydrogen bonds between a peripheral and an integral membrane protein
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Integral membrane proteins
- Distribution of membrane proteins: variable composition of the inner and outer membrane surface
Examples of asymmetrically distributed membrane components | ||
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Integral membrane proteins | Transmembrane proteins |
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Integral monotopic proteins |
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Peripheral membrane proteins | Extracellularly directed |
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Intracellularly directed |
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Because of their fluidity, membranes are also permeable to water and some small molecules like O2, even without the use of specific channels or transporters. This characteristic is termed semi-permeable!
Glycocalyx
- Definition: loose glycoprotein-polysaccharide layer covering the outside of the cell membrane in some eukaryotic and prokaryotic cells
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Structure
- Long, branching network of polysaccharides
- Covalently bound to proteins and, to a lesser extent, lipids of the cell membrane
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Function
- Protects the cell from dehydration
- Antigenic function
- Enables immune cells to differentiate between host cells and foreign organisms
- At the RBC membrane: differentiation of blood groups
Membrane functions
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Protects the cell from the external environment
- Cell membrane: separates the cell from the external environment
- Membrane of cell organelles (endomembrane system): separates cell compartments within the cytosol
- Transport of substances from the inside to the outside of the cell or from the outside to the inside of the cell
- Signal transduction: conversion of extracellular signals into intracellular reactions
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Cell identification
- Every cell expresses specific proteins on its surface that are mostly glycosylated (glycoproteins).
- These glycoproteins are highly specific for each cell type and allow for the distinction of self cells from one another as well as from foreign cells.
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Electrical excitability
- Generation of an electrochemical gradient across the membrane creates a membrane potential.
- Excitation activates voltage-gated ion channels, temporarily decreasing the negative membrane potential (depolarization).
- Cell junctions: : formed by anchor proteins (cell adhesion molecules), which are anchored to the cytoskeleton and protrude outside of the cell
Cell organelles
Cellular organelles are compartments within cells that are enveloped by a membrane and have a highly specific function. Eukaryotes contain numerous organelles, whereas prokaryotes lack compartmentalization.
Overview of the most important cell organelles | ||
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Cellular organelles | Structure | Function |
Nucleus |
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Endoplasmic reticulum (ER) |
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Golgi apparatus |
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Mitochondria |
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Lysosomes |
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Peroxisomes |
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Cell nucleus
Structure
The nucleus is the control center of the cell. It is surrounded by a double membrane and contains all of the cell's genetic material except mitochondrial DNA.
Nuclear envelope
The nuclear membrane consists of an inner and outer membrane, each composed of a lipid bilayer.
- Outer nuclear membrane: contains numerous ribosomes
- Inner nuclear membrane: covered by the nuclear lamina, a network of intermediate filaments (lamina) that has a stabilizing effect
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Nuclear pores: The inner and outer nuclear membranes fuse at some points and form nuclear pores with the aid of large protein complexes.
- Function
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Proteins involved: Ran proteins
- Small G protein and important mediator of the nuclear import and export of proteins
- In the GTP-bound form, Ran proteins bind to importins in the nucleus → complex of Ran + importin + protein transported into the nucleus from importin → release of transported proteins from the transport receptor importin
Nuclear content
- Chromatin: complex of DNA, histones, and nonhistone proteins
- Nucleolus: site of rRNA synthesis and ribosomal subunit assembly
Functions
- Storage of the entire genetic information of an organism in the form of chromatin (except mitochondrial DNA)
- Duplication of genetic information before cell division (DNA replication): see the cell cycle for further information
- Transcription: initial step of protein synthesis
- Synthesis of rRNA in the nucleolus
- Packaging and protection of inactive DNA by histones
Endoplasmic reticulum
The endoplasmic reticulum (ER) is an extensive network of membranes that is directly connected to the outer nuclear membrane. The ER forms a channel system of elongated cavities. The most important function is the synthesis of cellular components and cell export products. The ER can be microscopically and functionally differentiated into the rough and smooth ER.
Structure
- Membranous channel system
- In direct contact with the outer nuclear membrane
- Composed of two microscopic and functionally different regions
- Rough endoplasmic reticulum (rER): ribosomes bound to the surface
- Smooth endoplasmic reticulum (sER): lack ribosomes
Functions
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rER
- Synthesis of membrane, secretory, and lysosomal proteins (translation)
- Packaging of newly synthesized proteins into vesicles to transport to the Golgi apparatus (for further processing) or directly to a specific location
- Staining of negatively charged ribosomes with cationic (basic) dyes, e.g., rER appears as Nissl bodies in the soma and dendrites of neurons (light microscopy)
- Cells rich in rER include cells of the exocrine pancreas and plasma cells
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sER
- Synthesis of phospholipids, fatty acids, and steroids
- Carbohydrate storage and release of stored carbohydrates
- Biotransformation
- Calcium storage
- Cells rich in sER include cells of the adrenal cortex and the gonads, hepatocytes
Golgi apparatus
The Golgi apparatus receives vesicles, especially from the ER and is responsible for further distribution of the substances (proteins and lipids) to their specific target structure like the lysosomes or the cell membrane.
Structure
- Enveloped, disc-shaped, slightly curved vesicle system with two sides:
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Cis-Golgi face (convex side): bends slightly around the ER
- Function: Membrane vesicles from the ER that are loaded with proteins are received at the cis-Golgi face.
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Trans-Golgi face (concave side): towards the cell membrane
- Function: Vesicles are detached and sent towards the cell membrane and lysosomes.
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Cis-Golgi face (convex side): bends slightly around the ER
Functions
- Modification of glycoproteins and hormone precursors received from the ER as well as of membrane proteins recycled from the plasma membrane by endocytosis
- Activation of hormones and other proteins
- Sorting of proteins according to their target sequence or attached oligosaccharides
- Synthesis of lysosomes and their loading with enzymes
- Reprocessing of membrane components
Defective labeling of lysosomal acid hydrolases in the Golgi apparatus leads to I-cell disease.
Mitochondria
Mitochondria are often described as the “powerhouses” of the cell due to their central role in the synthesis of ATP, a vital source of energy for the body. They are composed of a double membrane, the intramembranous space, and the matrix. Various mitochondrial types can be differentiated according to the inner membrane structure.
Structure
The structure and DNA of mitochondria resemble those of prokaryotes. Mitochondria are believed to originally have been prokaryotes that evolved into endosymbionts living inside eukaryotes (see symbiogenesis).
Mitochondrial membrane
There are two, highly specialized mitochondrial membranes that surround the mitochondrion. They provide the framework for the electron transport chain and ATP production.
Outer membrane
- Structure: smooth
- Permeability: interspersed with pores, highly permeable for various molecules
Inner membrane
- Structure: convoluted
- Permeability: impermeable, especially to ions; however the inner membrane contains many different highly specific transport proteins
- Characteristic component: cardiolipin (stabilizes the enzymes of oxidative phosphorylation)
Carriers of the inner mitochondrial membrane
Specific transporters regulate the transport of substances through the inner membrane.
- Functional mechanism: antiporter of two molecules
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Examples
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Malate-aspartate shuttle : transport of reducing equivalents
- Cytosol: transfer of electrons from the cytosolic NADH onto oxaloacetate, resulting in the formation of malate (enzyme: cytosolic malate dehydrogenase)
- Transport of malate (in exchange with α-ketoglutarate) through the inner mitochondrial membrane using a carrier protein
- Mitochondrial matrix: reoxidation of malate to oxaloacetate through mitochondrial malate dehydrogenase resulting in the reformation of NADH
- Mitochondrial matrix: transamination from oxaloacetate in conjunction with glutamate into aspartate and α-ketoglutarate
- Transport of aspartate through the inner mitochondrial membrane in cytosol using another carrier protein in exchange with glutamate
- Cytosol: deamination of aspartate to oxaloacetate with simultaneous conversion of α-ketoglutarate into glutamate
- Carnitine-acylcarnitine translocase
- Glutamate aspartate transporter
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Malate-aspartate shuttle : transport of reducing equivalents
In the malate-aspartate shuttle, only the electrons of NADH and not NADH itself are transported across the inner mitochondrial membrane!
Mitochondrial matrix
- Contains mitochondrial DNA (mtDNA) and ribosomes responsible for the synthesis of ∼ 15% of the mitochondrial proteins
- The remaining mitochondrial proteins are encoded in the nucleus and are transported into the mitochondria in an unfolded state, where they take on their final folded structure.
Function
- Energy production: The inner mitochondrial membrane contains the enzymes of the respiratory chain and the ATP synthase that together produce ATP (oxidative phosphorylation).
- Other metabolic pathways in the matrix
- Initiation of apoptosis:
Symbiogenesis
The DNA and ribosomes of mitochondria resemble those of prokaryotes. The discovery of this produced the endosymbiotic theory of mitochondrial evolution, which states that mitochondria were originally independent prokaryotic bacteria with the special ability to produce energy through oxidative phosphorylation that were eventually engulfed by eukaryotic cells. As a result, the prokaryotic cells lost parts of their DNA and their ability to live independently, while the eukaryotic host cell became dependent on the energy produced by the incorporated bacterium.
Lysosomes
Lysosomes can be regarded as the cell's waste disposal system. Their main function is intracellular digestion, e.g., the degradation of polymers into monomers.
Structure
- Small spherical organelles that are surrounded by a lipid bilayer and filled with digestive hydrolytic enzymes responsible for the degradation of macromolecules.
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Hydrolytic enzymes: lipases, glucosidases, acidic phosphatases, nucleases, endoproteases (e.g., cathepsins )
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Origin of hydrolytic enzymes
- Enzymes are synthesized at the ribosomes of the rough ER and then transported to the Golgi apparatus.
- A mannose 6-phosphate molecule is attached to the enzymes post-translationally by N-acetylglucosaminyl-1-phosphotransferase in the Golgi apparatus.
- The enzymes tagged with mannose 6-phosphate are packaged into vesicles (primary lysosomes).
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Origin of hydrolytic enzymes
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Acidic environment (pH value of ∼ 5)
- Optimal pH value for hydrolytic enzymes
- Maintained by the active transport of H+ through the membrane H+-ATPase
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Hydrolytic enzymes: lipases, glucosidases, acidic phosphatases, nucleases, endoproteases (e.g., cathepsins )
The main enzyme of lysosomes is acidic phosphatase!
Function
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Intracellular degradation of macromolecules
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Process
- Primary lysosomes are vesicles with newly synthesized hydrolytic enzymes that bud from the Golgi apparatus.
- They fuse with vesicles, e.g. endosomes, phagosomes, that contain digestive materials and thereby form secondary lysosomes.
- The hydrolytic enzymes in the secondary lysosomes degrade the macromolecules.
- Cleavage products are emptied into the cytosol and can be reused for new synthesis processes.
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Residual bodies: lipid-rich, undigested material (lipofuscin) left over from macromolecule degradation is expelled from the cell or stored in the cytosol in residual bodies.
- Intracellular lipofuscin deposits (yellow-brown pigmented granules) accumulate in neurons, hepatocytes, and cardiomyocytes with age.
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Origin of macromolecules
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Endocytosis
- Receptor-mediated endocytosis: endocytic vesicles from the plasma membrane fuse first with early endosomes and later with lysosomes
- Phagocytosis : Particles are engulfed and taken up by phagocytic cells thereby forming phagosomes.
- Autophagy: Autophagosomal membranes fuse and form an autophagosome that sequesters intracellular debris, e.g., proteins, lipids, cell organelles. It later on fuses with lysosomes for degradation of the macromolecules.
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Endocytosis
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Process
- Autolysis: In the event of severe cellular damage, lysosomes release their contents into the cytosol, causing the cell to disintegrate (apoptosis)
Lysosomes play an important role in adaptive immunity. Antigen presenting cells (e.g., macrophages, dendritic cells) internalize antigens and degrade them by proteolysis within lysosomes. Afterwards, the resulting peptides are loaded onto MHC class II molecules, delivered to the cell surface and presented to naive T cells.
Peroxisomes
Peroxisomes are spherical organelles surrounded by a single membrane. They contain enzymes that oxidize amino acids and fatty acids utilizing oxygen.
Structure
- Relatively small, round, membrane-enclosed vesicles
Function
- Degradation (beta-oxidation) of very long chain fatty acids up to octanoyl-coenzyme A (CoA) (eight carbon atoms)
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Degradation of hydrogen peroxide
- The mono-oxygenases convert their substrate using molecular oxygen.
- The resulting cytotoxic hydrogen peroxide (H2O2 ) is converted to water and oxygen (2 H2O2 → 2 H2O + O2) by catalase.
- Biosynthetic function: Sub-steps of, e.g, steroid hormone synthesis, bile acid synthesis, and plasmalogen formation
In Zellweger syndrome, peroxisome formation and function is impaired, leading to the accumulation of cytotoxic hydrogen peroxide.
Cytosol and ribosomes
Cytosol
The cytosol, also termed matrix, is enclosed by the cell membrane. In prokaryotes, almost all metabolic pathways occur directly in the cytosol, whereas in eukaryotes, several of these processes occur in cell organelles that are separated from the cytosol by a membrane (compartmentalization).
Structure
- Water, dissolved ions, and small molecules (70%)
- Proteins, e.g., enzymes involved in metabolic pathways (30%)
Function
- Metabolic processes (e.g., glycolysis, translation, protein degradation)
The cytoplasm surrounds the nucleus and consists of the cytosol and the cell organelles.
Ribosomes
Ribosomes are very large molecule complexes of RNA and proteins, which are located in the cytosol, on the cytosolic side of the rER and within the mitochondria. The ribosome is the site of protein synthesis (translation).
Structure
- Structure
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Mass: The mass of the ribosomal subunits is measured using the sedimentation coefficient (unit: Svedberg, S).
- Small subunit: 40S in eukaryotes, 30S in prokaryotes
- Large subunit: 60S in eukaryotes, 50S in prokaryotes
- Total mass : 80S in eukaryotes, 70S in prokaryotes
Localization
- Cytosolic ribosomes: Free ribosomes in the cytosol or bound to the cytoskeleton
- Membrane-bound ribosomes: bound to the rER
Function
- Translation: Ribosomes constitute the structural prerequisites for protein synthesis and are catalytically active. The RNA components of ribosomes (rRNA) interact with mRNA and tRNA and catalyze peptide bond formation.
Cytosolic proteins (such as tubulin) are synthesized on free ribosomes. Lysosomal and membrane proteins are synthesized on ribosomes of the rER!
Cytoskeleton
The cytoskeleton is a network of filaments extending throughout the cytosol.
Overview
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Functions
- Stability and movement of the cell and its organelles
- Transport processes within the cell
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Structure: composed of filaments and accessory proteins
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Filaments: elongated cell structures composed of monomers
- RBCs contain a special kind of cytoskeleton filament on the cytosolic side of their cell membrane that consists of the filamentous protein spectrin. If forms a meshwork with other proteins like band 3, ankyrin, and band 4.1 proteins.
- Accessory proteins: responsible for various functions of the cytoskeleton (motion, attachment and detachment of monomers, etc.)
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Filaments: elongated cell structures composed of monomers
The most important cytoskeletal elements
Filament | Structure | Accessory protein | Function |
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Actin filaments (Microfilaments) |
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Intermediate filaments (IFs) |
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The spectrin-based cytoskeleton of RBCs is deficient in hereditary spherocytosis.
Intermediate filaments can be used as immunohistochemical tumor markers to detect the origin of a neoplasm.
Cell junctions
The cells of the body are connected to other cells and the surrounding structures by cell-cell junctions and cell-matrix junctions. The type and number of junctions varies between different cell types. While red blood cells do not form cell junctions, epithelial cells are tightly connected to one another and with the basal lamina.
Occluding junctions
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Tight junction (zonula occludens): Sealing contact that forms an intercellular barrier between epithelial cells.
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Structure
- Membrane proteins (claudins and occludins) of two cells interact.
- Connected to actin filaments of the cytoskeleton via adapter proteins
- Localization: usually at the apical surface between epithelial cells
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Function:
- Seals adjacent epithelial cells together and thereby separates the apical from the basal side of the epithelium.
- Prevents the paracellular transport of ions and molecules
- Serves as diffusion barrier
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Structure
Anchoring junctions (adhering junctions)
Anchoring junctions are mechanical attachments between cells. Several forms can be differentiated depending on function.
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Desmosomes (macula adherens, spot desmosome): linking of two cells with support by IFs
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Structure
- Intermediate filaments radiate intracellularly and cadherins (mainly desmoglein and desmocollin) extracellularly from the desmosomal plaque, which is located on the cytoplasmic side of the cell membrane.
- Cadherins connect the desmosomal plaques of two cells.
- Occurrence/function: primarily connect cells subject to high levels of mechanical stress (e.g., epithelial cells and cardiomyocytes)
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Structure
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Hemidesmosome: does not connect two cells, but attaches cells to the extracellular matrix
- Structure: integrins connect the intracellular cytoskeleton (keratin) with laminin molecules of the basal lamina.
- Occurrence/function: connects epithelial cells with the basal lamina
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Adherens junction (zonula adherens, belt desmosome): tightly connects cells across a broader belt-shaped area
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Structure: Vinculin and catenin are located on the intracellular side of the cell membrane and connect the intracellular actin filaments with the transmembrane adhesion proteins such as cadherins (mainly E-cadherin).
- Cadherins: calcium-dependent transmembrane proteins responsible for adhesion of cells to other cells.
- Occurrence/function: connects, e.g., epithelial cells and endothelial cells in a continuous, belt-like manner.
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Structure: Vinculin and catenin are located on the intracellular side of the cell membrane and connect the intracellular actin filaments with the transmembrane adhesion proteins such as cadherins (mainly E-cadherin).
Communicating junctions
Communicating junctions permit the passage of electrical or chemical signals.
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Gap junction (nexus): intercellular channels that connect two cells
- Structure: formed by the interaction of the connexons of two neighboring cells
- Occurrence/function: primarily cardiomyocytes. Controls the passage of electrical stimulus in cardiomyocytes as well as epithelial and retinal cells.
- Synapse
Auto-antibodies directed against components of the cell junctions are formed in autoimmune blistering diseases, e.g., in pemphigus vulgaris (antidesmosome antibodies), in bullous pemphigoid (antihemidesmosome antibodies).