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structure of IgCAM
- immunoglobulin domain
- have fibronectin repeats-short transmembrane helical domain
- 2 beta sheets on top of each other
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where are IgCAMs found
in the immune system
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Cadherin
calcium dependent membrane proteins used for adhesion
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two types of Cadherin interactions
- heterophillic interaction between two different cadherins
- homophillic interaction between two identical cadherins
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job of cadherins
primary job to organize tissue during embryologic development using homophilic cell-cell interaction
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structure of cadherins
alpha helix, with EC globular beta sheet and intracellular short tail that mediates down stream signaling that activate cytoskeleton
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cadherin signaling in cytoplasm
cadherin binds beta catenin binds alpha catenin and binds actin cytoskeleton
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what is Rho and function
GTPase signaling causes contraction of actin
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what is rac and funtion
GTPases signaling causes assembly of actin at the other side of the cell
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structure of integrins
- heterodimers alpha and beta chains
- alpha - 18 different ones
- beta - 8 different ones
- about 20 combinations exist
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what do integrins bind to
- they bind RGD in fibronectin
- they bind RDD in type VI collagen
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How is specificity of integrins determined
determined by specific alpha and beta chain
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two types of signaling of integrins
Inside out signaling, outside in signaling
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inside out signaling of integrins
some ligand interaction inside cell causes structural change of EC domain which leads to unfolding of EC domain and increase its affinity for ligands
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signaling cascade of integrins inside the cell
talin bind to intracellular domain of integrin and induces actin assembly
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Integrin - paxillin signaling
integrin binds paxillin and activates SAC kinase and FAK kinase- induces actin formation on stress fibers
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4 Types of Cell-Cell Adhesion proteins
Tight junctions, adherence junction, desmosome, gap junctions
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tight junctions
- cell-cell junctions separates the top and bottom with ring of interconnected fibers
- separates apical and basal domain of cells
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molecule in the ring of tight junctions
claudins- a transmembrane
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structure of claudins
short, broad 4 alpha helices, N-C both cytplasmic
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signaling of claudin in the cytoplasm
bind ZO1, ZO2, ZO3 that interact w/ small GTPases and induces actin assmebly- lead to ring formation around the cell
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permeability of tight junctions
selectively permeable, broad range of selectivities (kidney and filtration, blood vessel -looser)
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tight junctions and diseases
- Heterobacterpylori - causes stomach ulcers by producing toxin that loosens epithelial lining by loosening tight junctions
- Cholerae - loosens tight junctions in the intestines
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what are adherence junctions
homphilic E-cadherins
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characteristics of adherence junction
- lower, larger, bulkier than tight junctions
- more permeable and mechanically stronger
- forms belt around circumference of the cell
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first molecule in development that causes tissue assembly
homophilic E-Cadherins (adherence junctions)
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signaling of adherence junctions
cadherins interact with catenins, activate small GTPases induces actin/myosin assembly, produce force
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desomosome (macula adherins)
looks liek adherence junction, but has single point connections, bound to intermediate filaments
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Desmosome intracellular signaling
desmo binds plakoglobin binds desmoplakin bind keratin intermidate filaments very strongly
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Gap Junctions
channel proteins that bind actin, channels between cells
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do all cells have gap junctions
nope
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type of cells that use gap junctions
- nerve to muscle and cardiac cells
- used for depolarization and fast transfer
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structure of gap junction
- a heterohexamer on two cells that join together
- ~14 nm
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molecules that can go through gap junction
- spherical proteins ~1kDa, ssRNAm ions, small stuff
- bidirectional and some unidirectional
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how are gap junctions regulated
regulated by specific ligands and voltage
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way to slow down ion flux of gap junctions
strong. negative charge along interior of channel, slows positive ions
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