The cell

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 as 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 with a cell or cells containing various specialized, membrane-bound organelles such as nuclei and mitochondria.

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 have a significantly more complex structure.

Prokaryotic cells do not have a nucleus.

Both prokaryotes and eukaryotes have cell membranes. The cell membrane provides a boundary between the outside environment and 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 in separation from cytoplasmic processes. Furthermore, most prokaryotic and plant cells possess a cell wall, which envelops the cell membrane, stabilizes, and protects cells from the outside environment.

Cell membrane structure

The cell membrane (or plasma membrane) is composed of an asymmetric lipid bilayer with embedded or attached membrane proteins. The synthesis of membrane components occurs in the smooth endoplasmic reticulum (SER).

Lipid bilayer

• Structure: consists of 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).
  • 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
• Characteristics
  • Permeability
    • Almost impermeable to polar molecules
    • Highly permeable to nonpolar molecules and water
  • Fluidity: The fluidity of the membrane lipid bilayer changes depending on the composition of bilayer and the temperature of the environment.
    • Unsaturated fatty acids increase membrane fluidity.
    • Cholesterol and glycolipids; (i.e., lipids with a carbohydrate attached by a glycosidic covalent bond) stabilize the membrane.
  • Diffusion (transport): 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.
    • 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. Examples include:
      • Glucose and fructose transport into cells via GLUT transporters
      • Transport of glucose from the blood into the pancreatic beta cell via GLUT2
      • Water transport via aquaporin channels in principal cells of the kidney
      • Bicarbonate reabsorption in the early proximal convoluted tubule
      • Reabsorption of urea in the inner collecting ducts via urea transporters
      • Calcium transport from the sarcoplasmic reticulum into the cytosol via voltage-gated calcium channels

Membrane proteins

• Definition
  • Proteins that are embedded in the lipid bilayer of membranes
  • Usually glycoproteins
• Membrane protein content in the lipid bilayer: 20–80%
• Types of membrane proteins
  • 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)
  • 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
• Distribution of membrane proteins: variable composition of the inner and outer membrane surface

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. Accordingly, they are described as semipermeable.

Glycocalyx

• Definition: loose glycoprotein-polysaccharide layer covering the outside of the cell membrane in some eukaryotic and prokaryotic cells
• Structure
  • Long, branching network of polysaccharides
  • Covalently bound to proteins and, to a lesser extent, lipids of the cell membrane
• 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

• 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
• 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 self cells to be distinguished from one another as well as from foreign cells.
• 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

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.

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 for the 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 (lamins) that stabilizes the membrane
  • Nuclear lamins provide mechanical support and are involved in various processes of the cell cycle (e.g., transcription, signal transduction, chromatin organization)
  • A mutation in the gene encoding for lamin A results in Hutchinson-Gilford progeria syndrome
• Nuclear pores: The inner and outer nuclear membranes fuse at some points and form nuclear pores with the aid of large protein complexes.
  • Function
    • Regulate substance transport between the cytosol and the nucleoplasm (nucleocytoplasmic transport)
    • Active transport of large proteins over ∼ 40 kDa (e.g., nucleoplasmins) and RNA mediated by importins and exportins

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

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): characterized by ribosomes that are bound to the surface
  • Smooth endoplasmic reticulum (SER): without surface ribosomes

Functions

• RER
  • Synthesis of membrane, secretory, and lysosomal proteins (translation) and their modification (e.g., N-linked glycosylation)
  • Packaging of newly synthesized proteins into vesicles to transport to the Golgi apparatus (for further processing) or directly to a specific location
  • All proteins found within cell organelles (e.g., Golgi apparatus, lysosomes, ER) have their origin in the RER.
  • Cells rich in RER include exocrine pancreas cells, antibody-secreting plasma cells, and mucus-secreting goblet cells.
  • Nissl bodies: the RER found in the soma and dendrites of neurons
    • Site of synthesis for peptide neurotransmitters that are transported to the presynaptic terminals
    • Nissl stain: a cationic (basic) dye used to visualize negatively-charged ribosomes on light microscopy
• SER
  • Synthesis of phospholipids, fatty acids, cholesterol, and steroids
  • Biotransformation of drugs, alcohol, and toxins in the liver
  • Storage and release of carbohydrates
  • Location of glucose 6-phosphatase
  • Calcium storage
  • Cells rich in SER include hepatocytes, and steroid-secreting cells (e.g., adrenal cortex or gonadal cells)

Structure

Enveloped, disc-shaped, slightly curved vesicle system with two sides:

• Cis-Golgi face (convex side)
  • Bends slightly around the ER
  • Membrane vesicles from the ER that are loaded with proteins are received at the cis-Golgi side.
• Trans-Golgi face (concave side)
  • Faces the cell membrane
  • Vesicles are detached from the trans-Golgi side and sent towards the cell membrane and lysosomes.

Functions

• Synthesis of lysosomes and their loading with enzymes
• Recycling of plasma membrane proteins via endocytosis
• Activation of hormones and other proteins
• Modification of glycoproteins and hormone precursors received from the RER
  • O-linked glycosylation: attachment of O-oligosaccharides to serine or threonine
  • Modification of N-oligosaccharides on aspargine after N-linked glycosylation in the RER
  • Phosphorylation: Mannose residues on glycoproteins (e.g., lysosomal acid hydrolases) are phosphorylated to mannose-6-phosphate, allowing them to be trafficed to lysosomes. (Defects in this process lead to I-cell disease.)
• Sorting of proteins according to their target sequence or attached oligosaccharides

Vesicular trafficking proteins

• COPI protein: trans-Golgi network (TGN) → cis-Golgi network (CGN) → endoplasmic reticulum (retrograde trafficking)
• COPII protein: endoplasmic reticulum → CGN → TGN (anterograde trafficking)
• Clathrin: formation of coated vesicles (endosomes) for transport within cells
  • Receptor-mediated endocytosis: plasma membrane forms endosomes (e.g., mediated by LDL receptor)
  • TGN can also form endosomes (endosomes can become lysosomes)

Defective labeling of lysosomal acid hydrolases in the Golgi apparatus leads to I-cell disease.

To remember that COPII facilitates anterograde (forward) transport from the rough endoplasmatic reticulum to the Golgi apparatus and COPI facilitates retrograde (backward) transport, think: “Two cops (COPII) go for (forward) a coffee to go (to the Golgi apparatus). One cop (COPI) goes back (backward) to the rough (rough ER) neighborhood.”

Structure

• Vesicular, membrane-enclosed cell organelles originating from the trans-Golgi face of the Golgi apparatus
• Subclassified into early and late endosomes depending on their stage of maturation

Function

• Intracellular sorting and transport system
  • Early endosomes
    • Internalize materials from outside the cell via plasma membrane invagination
    • Recycle receptors (e.g., LDL receptor) and transport them back to the cell surface membrane
    • Can receive vesicles from the Golgi apparatus and send them back
  • Late endosomes: fuse with lysosomes and thereby allow for lysosomal degradation of endosomal content

Mitochondria are often described as the powerhouses of the cell because of their central role in the synthesis of ATP, a vital source of energy for the body. They are composed of a double membrane, intramembranous space, and matrix. Various mitochondrial types can be differentiated based on the inner membrane structure.

Structure

The structure and DNA of mitochondria resemble the structure and DNA of prokaryotes. Mitochondria are believed to have been prokaryotes originally 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)

Types of inner mitochondrial membranes

• Mitochondrial cristae
  • Thin invaginations (cristae) of the inner membrane
  • Present in most cells
• Tubular mitochondria
  • Inner membrane forms tubules
  • Mainly in cells that produce steroids

Carriers of the inner mitochondrial membrane

Specific transporters regulate the transport of substances through the inner membrane.

• Functional mechanism: antiporter of two molecules
• Examples
  • Malate-aspartate shuttle : transport of reducing equivalents
  • Carnitine-acylcarnitine translocase
  • Glutamate aspartate transporter

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
  • Citric acid cycle
  • Beta-oxidation
  • Ketogenesis
  • Urea cycle
  • Pyruvate decarboxylation
  • Heme synthesis
  • Gluconeogenesis
  • Production of Acetyl-CoA
• Initiation of apoptosis: See section “Apoptosis” in the article on cellular changes and adaptive responses for more information.

“If you cite (cytoplasm) my article, I might (mitochondria) give you a HUG”: Heme synthesis, the Urea cycle, and Gluconeogenesis take place in both, the cytoplasm and the mitochondria, think: “If you cite (cytoplasm) my article, I might (mitochondria) give you a HUG”.

Heme synthesis, the urea cycle, and gluconeogenesis take place in both the cytoplasm and the mitochondria.

Symbiogenesis

The DNA and ribosomes of mitochondria and prokaryotes have many similarities. The discovery of this resulted in the endosymbiotic theory of mitochondrial evolution, which is that mitochondria were originally independent prokaryotic bacteria with the special ability to produce energy through oxidative phosphorylation and 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 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, which are responsible for the degradation of macromolecules
  • Hydrolytic enzymes: lipases, glucosidases, acidic phosphatases, nucleases, endoproteases (e.g., cathepsins )
    • 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 after their translation by N-acetylglucosaminyl-1-phosphotransferase in the Golgi apparatus.
      • The enzymes tagged with mannose 6-phosphate are packaged into vesicles (primary lysosomes).
  • Acidic environment (pH value of ∼ 5)
    • Optimal pH value for hydrolytic enzymes
    • Maintained by the active transport of H⁺ through the membrane H⁺-ATPase

The main enzyme stored in lysosomes is acidic phosphatase.

Function

Intracellular degradation of macromolecules

• Process
  1. Primary lysosomes are vesicles with newly synthesized hydrolytic enzymes that bud from the Golgi apparatus.
  2. They fuse with vesicles that contain digestive materials, e.g., endosomes, phagosomes, and thereby form secondary lysosomes.
  3. The hydrolytic enzymes in the secondary lysosomes degrade the macromolecules.
  4. Cleavage products are emptied into the cytosol and can be reused for new synthesis processes.
  5. 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.
• Origin of macromolecules
  • 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, forming phagosomes.
  • Autophagy: Autophagosomal membranes fuse and form an autophagosome that sequesters intracellular debris (e.g., proteins, lipids, cell organelles). It later fuses with lysosomes in order to degrade the macromolecules.

Lysosomes play an important role in adaptive immunity. Antigen-presenting cells (e.g., macrophages, dendritic cells) internalize antigens and degrade them through 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.

Autolysis

In the event of severe cellular damage, lysosomes release their contents into the cytosol, causing the cell to disintegrate (apoptosis).

References:^[2]

Peroxisomes are spherical organelles surrounded by a single membrane; they play a key role in fatty acid oxidation and the biosynthesis and degradation of specific molecules.

Structure

• Relatively small, round, membrane-enclosed vesicles

Function

• Fatty acid oxidation
  • α-oxidation of branched-chain fatty acids
  • β-oxidation of very-long-chain fatty acids (VLCFA) to octanoyl-coenzyme A (CoA)
• Hydrogen peroxide metabolism
  • Mono-oxygenases convert substrates using molecular oxygen which results in hydrogen peroxide synthesis.
  • Catalases convert cytotoxic hydrogen peroxide (H₂O₂ ) to water and oxygen (2 H₂O₂ → 2 H₂O + O₂), which protects the cell from reactive oxygen species.
• Biosynthetic function
  • Steroid hormones
  • Bile acids
  • Plasmalogen
    • A type of ether phospholipid found in cell membranes
    • Specific for white matter cells of the brain and cardiac myocytes
• Catabolic function: amino acids and ethanol metabolism

Zellweger syndrome is caused by impaired peroxisome formation, which results in the accumulation of cytotoxic hydrogen peroxide within the cells.

Refsum disease is caused by insufficient α-oxidation of branched-chain fatty acids.

Adrenoleukodystrophy is caused by insufficient β-oxidation of very-long-chain fatty acids.

Cytosol

The cytosol, also termed matrix, is part of the cytoplasm and enclosed by the cell membrane. In prokaryotes, almost all metabolic pathways occur directly in the cytosol. 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

• Glycolysis, hexose monophosphate shunt, gluconeogenesis
• Synthesis of nucleotides
• Translation, protein degradation
• Heme synthesis
• Urea cycle

The cytoplasm surrounds the nucleus and consists of the cytosol and the cell organelles.

Heme synthesis, the urea cycle, and gluconeogenesis take place in both the cytoplasm and the mitochondria.

Ribosomes

Ribosomes are very large molecule complexes of RNA and proteins that are located in the cytosol, on the cytosolic side of the rough endoplasmic reticulum (rER) and within the mitochondria. The ribosome is the site of protein synthesis (translation).

Structure

• Structure
  • Granular particle composed of RNA and proteins that form a small and a large subunit
  • Several ribosomes attached to one messenger RNA (mRNA) are termed a polysome.
• Mass: The mass of the ribosomal subunits is measured using the sedimentation coefficient (unit: Svedberg, or 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
  • Not attached to a membrane; can be found floating in the cytosol (free ribosomes) or bound to the cytoskeleton
  • Site of synthesis for a number of intracellular proteins (e.g., cytosolic and mitochondrial proteins)
• 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.

• Definition: a network of filaments (protein fibers) that extends throughout the cytosol.
• Functions
  • Stability and movement of the cell and its organelles
  • Transport processes within the cell
  • Essential for cell division
• Structure
  • 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. Spectrin forms a meshwork with other proteins (e.g., band 3, ankyrin, and band 4.1 proteins) .
  • Accessory proteins
    • Responsible for various functions of the cytoskeleton (e.g., motion, attachment and detachment of monomers)
    • Motor proteins: important accessory proteins responsible for filament motion

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.

To remember drugs that disrupt microtubules, think “Microtubules Get Constructed Very Poorly”: Mebendazole, Griseofulvin, Colchicine, Vincristine/Vinblastine, Paclitaxel.

Negative end Near Nucleus, while Positive end Points to the Periphery: The negative end of the microtubule is oriented towards the nucleus and the positive end is oriented towards the periphery of the cell.

Kin (keen) to go out (anterograde), Dying to come back home (retrograde). Kinesin transports anterograde (from – → +) along the microtubule. Dynein transports retrograde (from + → –) along the microtubule.

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 to the basal lamina.

Occluding junctions

• Tight junction (zonula occludens): sealing contact that forms an intercellular barrier between epithelial cells
  • 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
  • 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

Anchoring junctions (adhering junctions)

Anchoring junctions are mechanical attachments between cells. Several forms can be differentiated according to function.

Adherens junction (zonula adherens, belt desmosome)

• Description: tightly connects cells across a broader belt-shaped area
• Structure:
  • Vinculin and catenin are located on the intracellular side of the cell membrane and connect the intracellular actin filaments with transmembrane adhesion proteins such as cadherins (mainly E-cadherin).
  • Cadherins
    • Calcium-dependent transmembrane proteins responsible for adhesion of cells to other cells
    • Loss of cadherins is associated with metastatic transformation in neoplasias.
• Function: connects, e.g., epithelial cells and endothelial cells in a continuous, belt-like manner

Desmosomes (macula adherens, spot desmosome)

• Description: linking of two cells via intermediate filaments
• 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.
• Function
  • Primarily connect cells subject to high levels of mechanical stress (e.g., epithelial cells and cardiomyocytes)
  • Pemphigus vulgaris: autoantibodies against desmoglein 1 and/or 3

Hemidesmosome

• Description: : does not connect two cells, but attaches cells to the extracellular matrix
• Structure: : Integrins connect the intracellular cytoskeleton (keratin) with molecules of the basement membrane (laminin, fibronectin, and collagen).
• Function
  • Connects epithelial cells with the basal lamina and maintains the integrity of the basement membrane.
  • Bullous pemphigoid: autoantibodies against hemidesmosomes

Communicating junctions

Communicating junctions permit the passage of electrical or chemical signals.

• Gap junction (nexus): intercellular channels that connect two cells
  • Structure: formed by the interaction of the connexons of two neighboring cells
    • Connexon: composed of six membrane-spanning proteins (connexins) with a central pore
  • Occurrence/function
    • Primarily cardiomyocytes; control the passage of electrical stimulus in cardiomyocytes as well as epithelial and retinal cells
    • Chemical communication between cells with second messenger molecules (e.g., IP3, Ca²⁺)
• Synapse: areas where signals or action potentials are transmitted from a presynaptic to a postsynaptic structure (e.g., neurons, muscle)

Auto-antibodies directed against components of the cell junctions are formed in autoimmune blistering diseases, e.g., in pemphigus vulgaris (antidesmosome antibodies) and bullous pemphigoid (antihemidesmosome antibodies).

CADherins are CAlcium dependent ADhesion proteins.

• Zellweger syndrome
• Mitochondrial myopathies
• Lysosomal storage diseases
• Hereditary spherocytosis
• Tumor markers
• Autoimmune blistering diseases