LEC38: Cells in Tissues: Junctions, Adhesion, and Extracellular Matrix Flashcards
what is epithelia
majority of cell in body are epithelia
line channels on inside and outside of body - i.e. in pancreas, gut, skin
form sheets, display polarized structure, w/ apical border exposed or lining channel and basal surface on basal lamina
are epithalial cells polarized
yes
polarization maintained by specialized cell junctions that bind the cells to each other, help separate distinct membrane domains
kinds of cells in body
epithelia
connective tissue
muscle cells
nervous cells
blood cells
ell adhesion moecules
1) cadherins
2) IG superfamily
3) integrins
4) selectins
homophilic vs heterophilic binding
homophilic- same adhesion molecule binding (i.e. cadherins)
heterophilic- diff molecules (integrins on the cell, laminin on ECM)
cell adhesion molecule functions inside cells
1) inside cells, bind to adapter proteins that interact w/ cytoskeleton, thereby connecting outside of cell to cellular machinery:
binding regulates cell migration, cell proliferation, cell death
2) associate in clusters in a lateral fashion, creating junctions of cell adhesion molecules
ECM functions
1) hold tissues together - multiadhesive proteins
2) provide cushioning (cartilage) and strength (tendons) - via proteoglycans
3) acts as reservoir for growth factors
4) resist tensile/stretching forces via proteins like collagen
what comprises ECM?
proteins and carbohydrates such as proteoglycans
all ECM components are highly networked w/ each other, and w/ receptors on cell surface, i.e. integrins
composition of ECM varies by tissue
purpose of epithelial cells’ polarized cellular organization
divide body cavities, provide barriers between gut and blood and blood brain barrier
polarization allows for diff functions like absorption of nutrients on 1 membrane, secretion from another membrane
what is on apical surface of epithelial cells
villi
for absorption
cell junctions in epithelial cells
1) tight junctions
2) anchoring junctions: adherens, desmosomes, hemidesmosomes
3) communicating junctions: gap junctions
4) integrins
tight junctions function? structure?
exist directly under microvilli
seal epithelial cells together in sheets
prevents passage of small molecules
tight junctions made of?
claudins, occludins
anchoring junctions function
join cells to each other and to ECCM
1) adherens junctions and desmosomes
2) focal adhesions and hemidesmosomes
adherens junctions and desmosomes functions
made by homophilic interactions among cadherens
hold cells together by connecting to a linker protein, alpha and beta catenin, in the middle of cytoskeletons of 2 cells
impact polarity of epithelial cells also
nature of caderins throughout the body?
tissue specific localizations - diff kinds of cadherins in diff parts of the body
cancer cells can move throughout the body if/when they lose their specific cadherins
focal adhesions?
integrin proteins that bind to the ECM outside and attach to actin inside the cell
controls interaction of integrin w/ the ECM, outside of cell
impact physiological processes
desmosomes connect with what?
anchoring junctions that connect with cadherins and IF, so bind indirectly to actin
hemidesmosomes are made of?
IF
bind inside the cell, and to the ECM via integrin
gap junctions function?
cell - cell communication
allwo for electrical coupling between cells
what are cadherins
what does their loss result in
large glycoproteins that link by a homophilic (same cadherin) mechanism
link to actin cytoskeleton via adapter proteins, catenins (alpha and beta catenin)
disruption of cytoskeletal interaction via adapters -> loss of adhesion
integrins function
cell matrix receptors on cells
are abdunant on cell surfaces, bind ligand w/ low affinity
activate signaling pathways upon ligand binding
comprise alpha and beta subunits held together noncovalently
Ca2+ or Mg2+ needed for ligand binding
what integrain is a hemidesmosome connection
a6b4 interacts w/ IFs a hemidesmosomes
exception to integrins connecting to bundled actin filaments
what mediates actin-integrin interaction
anchor proteins - talin, a-actinin, filamin
linkage leads to clustering and formaiton of focal adhesions
what are selectins?
lectins (carb binding) that media Ca2+-dependent cell-cell adhesion in bloodstream
L-selectin in WBC, P-selectin in platelets
each binds to a specific carb on another cell
how do WBC travel around the blood
during inflammation, endothelial cells express E-selectin
as travel around blood, WBC bind to an epithelial cell via selectins (i.e. E-selectin), selectins collaborate w/ integrtins
WBC then roll over cells til get to integrins, where WBC are stopped, and go through endothelial cells and into tissue
so selectins mediate weak binding at first, integrins mediate strong binding to WBC
what is ECM
space between cells
a misture of proteins and polysaccharides
high ECM in bone and cartilage, low ECM in brain and spinal cord
what forms bone/teeth
calcified ECM
how is ECM in tendon
trannsparent
what is basal lamina
form of the ECM at interface of epithelia and connective tissues
where is basal lamina found
underlies epithelial cell sheets and tubes
around muscle cells, fat cells, schwann cells
separates these cells from CT and serves as highly selective filter
what does basal lamina influence
cell polarity, metabolism, survival, proliferation, idfferentiation
serves as highway for migration
what forms BL
cells that sit on it
what is basement membrane
structure connected to BL by type IV collagen to underlying CT
proteins of the BL?
type IV collagen
multiadhesive proteins, laminin
proteoglycan, perlecan
nidogen
these form a meshlike structure
laminin is?
heterotrimeric multiadhesive matrix protein found in all BL
interacts w/ integrins on 1 end, collagen on other end
helps integrate structures
most abundant protein in body?
collagen
ollagen structure
triple stranded helical conformation, forms a rope-like structure
can resist tensile forces
in tendons, are in parallel bundles, aligned along major axis of tendon
proteoglycan structure and function
type of GAG
hydrate to a high degree, become gel-like to resist compressive forces
easily form gels
how are collagen in bone, cornea?
arranged in parallel bundles that lie on top of other bundles at right angles
collagen XVIII is in basal laminae of blood vessels
Collagen XVIII cleavage -> endostatin, which inhibits angioenesis
what is fibronectin structure, function?
modular protein that binds to other matrix molecules and receptors on cells - binds integrins on 1 end, collagen on other end, integrates binding btwn them
structure, funciton of elastin?
found on skin, blood vessels, lungs
elastic fibers allow for recoil after transient stretch
rich in glycine, proline, hydroxyproline
sheated by microfibrils ocntaining fibrillin
what causes Marfan’s syndrome?
mutation in fibrillin I gene
fibrillin I usually binds to an intert form of TGF-beta, keeps it firmly inactive
patients w/ fibrillin I mutation means cells cannot form TGF beta in its inactive form, instead get overactive TGF beta and overactivity of the growth factor
leads to defects in tissues rich in elastic fibers, such as aorta, which is prone to rupture; loose joints, weakness in blood vessels, tallness
what re: fibronectin makes cancer cells more mobile
cancer cells make less fibronectin -> are more mobile
are not anchorage dependent
