Flashcards in 22 Cell Junctions Deck (58):
bone, tendon with plentiful extracellular matrix and cells with minimal distribution throughout
cytoskeleton of cells form anchoring junctions. mostly consistent of basal lamina
bon epithelial tissue to connective tissue
What are the four types of cell junctions?
cell-cell adhesion and cell-matrix adhesion connected to cytoskeletal filaments inside cell
closes gaps between epithelial cells
passageway for small, water-soluble ions
allow signal relay-between cells
Actin filaments participate in what attachment sites?
1. adherenes (cell-cell)
2. actin-linked cel-matrix adhesions ( cell-matrix)
Intermediate filaments participate in what attachment sites?
1. desmosomes (cell-cell)
2. hemidesmosomes (cell-matrix)
What is the role of transmembrane adhesion proteins?
1. anchoring junctions that span membrane, extending from cytosol to ECM
2. cadherins or integrins, selectins, Ig superfamilies
A classical cadherin is seen where?
1. adherens (cell-cell) junctions with actin filaments
A nonclassical cadherin is seen where?
1. desmosomes with intermediate filaments
Integrins are commonly found where?
1. actin-linked cell-matrix adhesions with actin filaments
Cadherins are what?
1. Ca ion dependent cell adhesion
2. classical: form adherens junctions
3. E-cadherin: epithelial cells and brain
4. nonclassical: desmocollins/desmogleins that form desmosome junction
Do cadherins bind homo or heterophilically?
homophilic ir preferred but heterophilic can occur
What does the presence/absence of Ca ion play in cadherins?
1. Ca present: binds in between the cadherins and increases rigidity of structure, preventing flexion
2. Ca absence: allows cadherin repeats to flex and bend
Cadherins have low affinity for their ligand, so how do they form strong attachments?
1. increase number of sites that are bound.
2. act like velcro
1. promotes cadherins, homophilic binding ability via segregation
2. provides ability for different tissue formation during development
Cadherins contain intracellular domains that allow what to attach?
1. beta-catenin, p120-catenin, gamma-catenin which provide a link between the cadherin and actin filaments
A contractile bundle of actin filaments lies adjacent to and adhesion belt in what structure?
adherens junctions, which shapes multicellular structures
What is the role of desmosomes?
1. mechanical support that binds to intermediate filaments
What is the structure that provides desmosomes the ability to bind strongly to one another?
1. plaque surface of multiple proteins that side-by-side interaction allow for mechanical strength
1. homo-/heterophilic binding to the inner dense plaque.
2. are transmembrane and form the outer dense plaque
3. bind to a belt of plakophilin and plakoglobin
The cell type determines the type of intermediate filament that is formed?
1. seals gap between cells
2. forms fence between membranes
3. recruits cytoskeleton and signaling molecules
Why do tight junctions appear as fusion of PMs?
1. focal connections between two PM correspond to connected sealing strands
What are two important proteins that help form tight junctions?
1. claudin (main function)
3. consist of 4 TM domains, C-/N- terminus are intracelular for signaling probably
What protein is responsible for controlling the position and organization of tight junctions?
1. ZO (Tip protein family)
2. controls anchoring of tight junctions to actin cytoskeleton
tradition thought of tight junction, but have diversified permeability. is extracellular
in the PM, that encircle the individual cells between apical and basolateral membranes.
- limit lateral diffusion
Signaling function of tight junctions
cytoplasmic region only. activate PDZ-containing proteins
What proteins are responsible for establishing cell polarity?
How is epithelial cell polarity established?
1. E-cadherins cluster, at cell-cell junction
2. AJ, TJ recruited to site of adherance
3.Par complex recruited to primitive adhesions to promote Par3-Par6-atypical protein kinase C assembly
What is the role of Par complex in adhesion formation?
1. par complex leads to activation of Crumbs and Scribble complexes to form other junctions
Where is Crumbs-3 mostly expressed?
1. epithelial cells as an apical membrane determinant
is the scribble complex intra- or extra cellular?
What is able to cause a gap junction to rapidly close that gated-channel?
1. rapid influx of Ca into a damaged cell, to isolate and protect other cells
What extracellular macromolecules are associated with the basal lamina?
1. fibrous protein(glycoproteins)
2. glycosaminoglycans (generally combine to form proteoglycans)
What is the basal lamina made of?
1. collagen type IV
1. alpha, beta, gamma
2. primary organizer of sheet
3. contain multiple bind sites for variety of compounds
Type IV collagen
1. provide tensile strength to basal lamina
2. consist of 3 super-twisted alpha helices
3. bind with laminin to form 2-D sheet
Nidogen and perlecan
1. linkers to connect laminin and Type IV collagen
What are integrins and dystroglycans used for in the basal lamina?
1. TM receptors
2. holds laminin feet to allow for coordination of other basal lamina components
What is the function of the thick basal lamina in the glomerulus of the kidney?
1. prevent macromolecule passage into blood
2. based on GAGs function as a filter
How can the basal lamina act as a selective barrier for cell movement?
1. prevents fibroblast in CT to contact epithelial tissue
2. permeable to macrophages, neutrophils, and proteases
What role does the basal lamina have in tissue regeneration?
1. acts as a scaffold for regenerative cells to adhere to and begin repair
What is an important structural feature of integrins?
1. short C-tail intracellularly, long N-terminal extracellularly
2. alpha-beta heterodimer
What intracellular protein is required to link the integrin tails to actin
talin, which binds to beta subunit
What type of integrin is most prominent in hemidesmosome adhesion?
1. alpha6beta4 which attaches to keratin filaments from plectin and dystonin
What defects would be prevent to produce a skin blistering disease?
1. loss of plectin, dystonin, alpha6beta4, causing loss of skin attachment to the basal lamina
Outside-in activation of integrin
1. ligand binds to the ECM region. causing conformatin change
2. conformation shifts alpha-beta units further apart allowing talin to bind beta unit
3.actin filament then bind to talin unit
Inside-out activation of integrin
1. PIP2 promotes translocation of talin to the beta subunit
2. binds to beta chain, causing conformational separation of units
3. causing extension of ECM region, increasing affinity for ligands
4. under influence from other signaling methods of the cells. (GPCR, RTK,)
What is the central signaling module downstream from integrins?
Src/FAK complex which causes ERK/JNK regulation for cell survival, proliferation, differentiation
What is the function of Focal adhesion kinases?
1. promote cell fluidity; breakdown focal adhesion
2. cancer have increased FAK, to provide higher level of mobility
What are the different types of glycosaminoglycans?
1. chondroitin sulfate
2. dermatan sulfate
3. heparan sulfate
4. keratan sulfate
What is the function of the glycosaminoglycans?
1. mechanically support tissue and withstand compressive forces
2. high cation concentration, attracts water to the area, providing resistance to compression