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Extracellular - Coggle Diagram

- - - - found in many stable tissues and link intracellular actin cytoskeletons
      - associated with initial contact between cells during tissue formation
      - extrusion of apoptotic cells triggered by loss of adherens and contraction of actin ring
      - circumferential belt of actin and myosin with adherins functions as atension cable that can internally brace the cell and control the shape
    - - adhesion controlled by family of trans-membrane proteins called cadherins
      - connects to actin cytoskeleton inside the cell
      - E-cadherin is the intracellular adaptor proteins that mediate actin binding
      - F-actin- A-catenin - B-catenin- E-cadherin; when this complex is subjected to mechanical stress, the C-terminal actin binding domain of a-catenin changes conformation and binds tighter to actin and uncovers a-catenin's adhesion modulation domain so additional F-actin filaments can be recruited
      - inhibiting Arp2/3 disrupts adherens junctions
  - - - Mice without desmoplakin die in early embryonic development
      - some rare inherited heart conditions are caused by desmoplakin mutations
      - desmoglein identified using skin disease pemphigus vulgaris which disrupts adhesions
  - - - form a seal between cells
      - prevents movement of water between cells
      - restrict movement between membrane lipids and proteins in polarised cells from basolateral to apical surface
      - regulate trans-epithelial transport and restrict movement of membrane lipids and proteins since they prevent paracellular movement
      - prevent movement of molecules which can only pass through cells (transcellular pathway)
      - bundles of intermediate filaments run parallel to cell surface and connect demosomes and hemidesmosomes creating rigidity
      - Transcellular pathway
        
        since many nutrients cannot pass through epithelium they move via membrane bounf transport proteins
        
        some claudins pack extracellular domains forming paracellular channels which allows some cmall molecules to move in via paracellular pathway (for example in some murine embryos)
    - - form strong interactions that bring adjacent membranes into close contact and have strong interactions with membrane due to it being a multipass integral protein
      - C-terminus tails bind to adaptor protein which link to actin cytoskeleton to stabilise tight junctions
      - tight junctions proteins have different extracellular domains that create different permeabilities
      - particular combinations enable selective permeability between cells
    - - these are examples integral membrane proteins in tight junctions
      - they have 4 membrane spanning a helices and are representative
      - there are others involved like junction adhesion molecules,and coxsackievirus and adenovirus receptor contain a single a helix
      - JAM, occludin and claudin extracellular domains form extremely tight links creating the seal
    - - when claudin-6 is engaged in intracellular tight junctions the cytoplasmic domain intiates kinase signallign resulting in activation of nuclear receptors
      - Also the C terminal of occulin binds to PDZ domains in some adaptor proteins, these proteins often serve as scaffolds which other proteins assemble
      - PDZ domain proteins are associated with tight junctions including ZO proteins which interact with occludin, claudin and other adaptor and signallling proteins, abd mediate actin association; these interactions stabilise occludin and claudin interactions
  - - - ions (like in neuronal tissue and cardiac muscle)
      - low weight precursors of cellular molecules (1.2kDa pass freely and larger than 2kDa do not)
      - products of intermediate metabolsim
      - small signalling molecules (like Ca2+)
    - - mutations can cause at least 8 human diseases
      - form of deafness, progressive degeneration of peripheral nerves and heart malformations
    - - these are intracellular membrane channels that enable communication (since plant wall prevents it)
      - plasma membranes merge to form a continuous channel
      - cytoskeletal filaments may continue through plasmodesmata
      - viruses and signalling molecules pass
      - may contain an extension of ER and think ER can pass through them
    - - vertebrate gap juncitosn are composed of connexions, they are transmembrane proteins and xonsist of 12 noncovalently associated connexin molecules (6 form cylindrical hemichannel called coonexon)
      - They form a continuous aqueous channel between cells
      - permeability of gap junctions is regulated by post translational modifications to connexins, example- for contraction of uterus there is 5-10x increase in connexin in smooth muscle cells and increase in number and size of gap junctions, reversed postpartum
      - Their assembly and transport depends on N-cadherin and associated proteins and desmosomal prteins. PDZ domains in ZO-1 and ZO-2 bind to C terminal of Cx43 adn mediate interaction with catenins and N-cadherin
- - - - polysaccharide chains
      - usually found attached to proteins to form proteoglycans
    - - collagens for mechanical strength
      - fibronectin to stick proteins together
      - elastic fibres in some tissues to provide stetchability
  - - - kinks to intermediate filaments and actin
      - consists of inner and outer plaque
      - integrin α6β4 heterodimer are transmembranal proteins, the cytosolic B4 chain binds to specialised adaptor proteins which interact with keratin based filaments
      - link ECM to cytoplasmic keratin intermediate filaments (in skin) cia plakins (plectin and BP230)
      - a single B subunit can interact with several achains in combinatorial diversity which allowing diverse functions
    - - keratin intermediate filament inside the cell and integrin extracellular domain is outside the cell
      - plectin and BP23o are in the plasma membrane
      - laminin is an adaptor protein that links to integrins and then links to the ECM
      - they comprise integral membrane proteins linked via cytoplasmic adaptor proteins (e.g. plakins) to keratin based intermediate filaments; principal adhesion receptor is integrin a64)
  - - - laminins
      - Type IV collagen
      - Nidogens
      - heaparin sulphate proteoglycans (perlecan)
      - attached to cells via hemidesmosomes
      - these are all will consefved in most organisms because of their crucial roles
    - - Epithelia- tight network underneath cells
      - muscel myotubes- extended muscle cells stuck together by ECM
      - kidney glomerulus- thick BM that links to podocytes for filtration
    - - it forms forms network with T4 collagen and other proteins to form BM
      - the cell is anchored to the BM by integrins
      - it binds to other ECM elements like collagen, and binds to cellssurface receptors like integrins
- - - - cleaved signal peptide
      - hydroxylation of Pro and Lys to give hydrophobic properties
      - glycosylation of some hydroxyl-Lys and Asp residues
      - disulphide bind formation leads to trimer foundation (protected by chaperones) (disulphide bonds are required for mechanical stress)
    - - trafficked through Golgi (in cisternal progression)
      - association of procollagen
      - procollagen trafficked to plasma membrane then exocytosis
    - - cleavage of properties from N and C termini by procollagen N-proteases and procollagen C-proteases
      - fibril self assembly via crosslinks via hydroxylysines and hydroxyprolines (catalysed by lysyl oxidase)
      - assembled with other collagens and proteioglycans
- - - - single transmembranal domain
      - realtively short C-terminal cystolic domain
      - 5 extracellular cadherin domains (EC1-5) and are used for Ca2+ binding and cell-cell adhesion
      - binding of 3 Ca2+ ions at each extracellular domain stabilises the extracellular domain, binding of EC1 domain to another EC1 is responsible for trans binding (Kd for this shows relatively weak binding)
      - cis and trans binding
        
        Ca-dependent curvature of 5 extracellular domains allows orientations of EC1 and EC2 domains
        
        for cis interactions, binding of 1 EC1 to complementary surface on EC2 on adjacent molecule on same membrane
        
        for trans binding of EC1 to EC1 of other cadherin on adjacent cell, this is stabilsised when a small segment of protein at N-terminus of each of 2 EC1 domains swings out and replaces the equivalent segment from its binding partner
    - - play role in tissue differentiation, since during differentiation relative amounts change
      - normal tissue recognition during morphogenesis is accompanied by conversion of non motile cells into mensenchymal cells (motile); this transition is accompanied by reduction in E-cadherin
      - cell-cell contact inhibits cell proliferation, and so when an established epithelium is formed there is no need for further division