lect 7: cellular interactions Flashcards
what are the learning objectives of this lecture?
cell-ECM interactions
-key cellular protein involved in cell-adhesion (integrins)
-integrin role in cell adhesion and transmembrane signal transduction (hemidesmosomes)
cell-cell interactions
-describe cadherins-based cell-cell interactions (adherens junctions, desmosomes)
-structure and function of tight junctions
-structure and function of gap junctions
how do interactions of cell with ECM work?
-cell surface receptors can bind to ECM components such as fibronectin, laminin, proteoglycans, and collagen (integrins interact with these)
most important of these receptors is integrins
-only in animal cells
-surface of all vertebrate cell types (in plasma membrane so therefore transmembrane)
-human have 24 types, each with specific functions that recognized different extracellular molecules
what is the structures of integrins?
glycoproteins
-have 2 membrane-spanning polypeptide chains: alpha and beta chains so they are considered heterodimer (bc 2 different subunits)
-2 conformations: bent=inactive form, upright=active form (can now bind to different components of ECM)
what are the main functions of integrins?
couple the matrix outside a cell to the cytoskeleton inside it
1. cell adhesion
-ECM (link ECM to cytoskeleton which is inside)
-other cells (can also link other cells)
2. signal transduction (to or fro plasma membrane)
-outside-in
-inside-out
what are the two types of signaling of integrins?
what is the signaling example of outside-in signaling? (talin)
talin
-integrin->talin->actin
-actin polymerization
what is another outside-in signaling example?
cytoplasmic tyrosine kinases (kinases are anything that adds a phosphate group)
-FAK (focal adhesion kinase)
-Src (proto-oncogene tyrosine-protein kinase)
-activation-> phosphorylate other proteins
-just know multiple different pathways that can be affected
what do outside-in signals influence?
outside-in signals influence cell
-differentiation
-motility
-growth, survival
normal vs. malignant
-normal: survive cultured on solid substratum (integrin-binding)-> die in suspension
-malignant: can grow in suspension->integrin independent (dont need binding to basement membrane, so why they can move and metastasize easily)
what is the integrin binding sequence?
RGD amino acid sequence (arginine-glycine-aspartic acid) is specific chain that integrin recognize
-this sequence is found in fibronectin, laminin, and other proteoglycans
what do cell-cell junctions do ?
protein structures that physically connect cells
1. increase cell communication
2. increase tissue structure
3. increase transport between cells
4. create impermeable barrier for certain substances
only found in immobile cells (point is to keep them together)
-alot found in epithelial tissues (e.g. skin, GI, lungs)
-epithelial cells face external world
what are the arrangements of epithelium?
-simple=1 layer pf cells, so columnar, squamous and cuboidal
-stratified=many layers, named after physiology of outermost layer
-squamous: flat and squished down
epithelial sheets are ________ and rest on a _____________
epithelial sheets are polarized (diff parts have diff functions) and rest on a basal lamina
what are the functions of the basement membrane?
doesn’t just support cells (does more than 1 thing)
-allows epithelial cells to physically attach to underlying connective tissue and offers structural support for epithelial repair and regeneration
-establishes the polarity of epithelial cells and serve as a barrier limiting invasion of epithelial tissue into underlying tissues
-ensures the nourishment and the exchange of materials and metabolites with the epithelial which are avascular
-acts as a selective barrier or permeability filter regulating the passage of substances between epithelium and supporting tissue, or from one compartment to another in specific locations
-plays an important role in cellular processes such as cell adhesion, migration, differentiation and proliferation
what is the graph summary of cellular interactions?
what are hemidesmosomes?
composed of integrin
-bind intra and extra cellular components
-extracellular: bind laminin in basement membrane
-intracellular: linker proteins (keratin)
what are tight juntion?
sealing the extracellular space
-seal adjacent-cell plasma membranes (apical sides)
-prevent passage of H2O, small proteins and bacteria
-selective permeability (only very small ones reach basal region)
what are the major proteins in tight junctions?
transmembrane proteins
-claudins (interact with eachother to form tight seals)
-occludins
what are cadherins?
cytoskeleton-linked junctions bind epithelial cells to each other
-membrane glycoprotein family
-join cells of similar type together
-possibly the single most important factor in molding cells into cohesive tissues in the embryo and holding them together in the adult
-cadherin loss is associated with malignancy (metastases)
what do cadherins play a role in?
role in adherens junctions and desmosomes
-provide structural continuity, tensile strength and link cells to form tissues
what is cadherins role in adherens junctions?
-anchor cells together, provide strength
-linked via actin (cytoskeletons)
3 major components of adherens junctions
1. actin filament: provide cellular shape
2. protein plaques: anchor membrane and binds to actin
3. cadherins: attach to protein plaques, connect to cadherins on other cells
what do adherens junctions form?
ADHESION BELTS
what is cadherins: role of desmosomes?
linkage of specialized cadherins
-desmoglein
-desmocollin
cytoplasmic side
-bind indirectly to intermediate filaments (keratin)
strong cell adhesion
-epidermis of skin
what can a dysfunction of desmoglein cause?
disrupts junctions (so not tight)
-called pemphigus vulgaris
-causes severe blistering
what are gap junctions?
intercellular communication
-connect adjacent cells: cytosol is continuous between cells
-electrical, metabolic coupling
formed by connexin
-integral membrane protein
-4 transmembrane domains
-form multi-subunit complexes
-create pores
-important in cardiac cells because allows electrical coupling so the communication is much faster
