EXAM1_L7_Cell_junctions_ECM Flashcards
what do actin filaments link to? other functions?
Link to basal lamina, adherens junctions, focal contacts. maintains cell shape
what do intermediate filaments attach?
attach to each other and the basal lamina
- desmosomes, hemidesmosomes provide mechanical strength to cells/tissues
what main function of microtubules?
molecular trafficking
what do adherens junctions attach? what made of?
attach actin cytoskeleton of two adjacent cells. made of cadherins
what do desmosomes connect?
connect intermediate filaments of adjacent cells
Cadherins (ecadherin)
transmembrane proteins that bind to each other across the extracellular space to form an adherens junction.
cadherins overlap each other- calcium for binding
What are the protein components and structure of adherens junctions?
If no calcium? if adherins failed? if no adhesion belt?
If protein not formed/not function?
Cadherins bound via A-CATENIN, B-CATENIN, & P120 to Actin cytoskeleton forming ADHESION BELT.
MAKES THE STRUCTURE OF EC’s
dysfunction would separate/break ec’s
is p120 missing or catenin? Ruin cell shape/structure/funciton.
What are 2 velcro protein components of desmosomes?
3 Proteins that connect Intermediate filaments to velcro proteins? Function overall?
Desmoglein & Desmocollin (bind to each other across ecs)
PLAKOGLOBIN/PLAKOPHILIN/DESMOPLAKIN link Intermediate filaments to velcro strands (desmoglein/collin)
Desmosomes link intermediate filaments of cells making structural stable network.
PREVENTS tearing/shearing of TISSUES
what could happen if claudin/occludin loosened by bacteria?
lose membrane polarity, transcellular transport interrupted, no barrier, lose gradients, na-k pumps futile- na dependent pumps stop working- loose glucose intake. Why? because molecules could then flow freely between the cells
What can pass through gap junctions? what is protein unit
6 connexins>1 connexon
Hemidesmosomes link what?
Collagen (laminin) of basal lamina to intermediate filaments (keratin) inside EC’s (no demoglein/collin)
Focal contacts/adhesions link what?
actin in EC’s to basal lamina LAMININ or COLLAGEN via fibronectin
What is common to focal adhesions and hemidesmosomes?
Integrins
what is an example of EC’s linking intracellular filament networks to protein components of basal lamina? What is key protein to make this work? what happens if not there?
hemidesmosomes- intermediate filaments to laminin
focal adhesions- actin network to laminin
Integrin- if not there- could have separation of ec’s from basal lamina
Integrin
Alpha/beta dimer- link actin cytoskeleton to laminin or collagen (depending on a/b dimer pair) in focal adhesions
-link keratin intermediate filaments to ecm protein laminin. called hemidesmosomes
Match : Focal adhesion or Hemidesmosomes
laminin/collagen; laminin only. keratin intermediate filament actin
Focal adhesion- laminin/collagen to actin via fibronectin
Hemidesmosomes-laminin : keratin/intermediate filaments
Laminin
large-flexible-disulfide bonds-abg chains- bind each other or collagen- sheets/network
Type IV collagen
non-fibrillar-3 protein strands- bind each other or laminin- forms mesh of collagen
Fibronectin
Only outside cell> V shape> two polypeptides (disulfide bond)> binding domains for Integrins (cell binding), collagen fibers, proteoglycans.
can assemble into fibers. role in adherence BL to EC’s
what connects collagen fibers to actin filaments via integrins?
Fibronectin AND Focal adhesions
if we are talking fibronectin what kind of adhesion is it?
Focal adhesion - BL to Actin via fibronectin
What 4 proteins are located in the ECM?
- COLLAGEN- strength
- ELASTIN-
- PROTEOGLYCANS (protein core w/ GAG’s) water
- HYALURONAN
Cells of ECM?
Macrophage, Mast cells, fibroblasts,
Collagen fibril stages
procollagen woven>tropocollagen aligned>collagen fibril bundles> collagen fiber
- PERIODICITY in type 1 only (fibrils fibers bundles)
type 2 & 3 fibrous
5 steps in fibrillar collagen formation inside of cell
- pro-a-chain polypeptide translated in ER
- hydroxylation of aa’s (proline/lysine) > hydroxyproline/lysine
- hydroxylysine residues glycosylated
- 3 pro-a-chains self assemble>procollagen triple helix
- > secreted into ECM
Steps in fibrillar collagen formation in ECM
- loose ends cleaved-=>tropocollagen
- tropocollagen self-assemble stagrd> Fibril
- fibrils assemble> fibers
What causes self assembly of tropocollagen into fibers?
Tropocollagen is 1000x more hydrophobic than procollagen-
Why can’t type IV collagen form fibrils?
cleavage of the triple helix polypeptides can’t occur on type IV collagen (basement membrane component)
What structural component makes collagen so strong?
repeating sequences of glycines, prolines, and hydroxyproline residues create KINKS enable strands to interlock in the triple-helical structure
What two enzymes require vitamin C? Why? Where?
Prolyl and Lysyl hydroxylase req. VitC because prolyl hydroxylase modifies proline residues of collagen to make hydroxyproline and VitC required for enzyme to be ACTIVE.
Hydroxylation of procollagen occurs in the ER
what forms the inter & intramolecular crosslinks within and between tropocollagen molecules that makes it so strong?
Where does this occur?
Lysyl Oxidase catalyzes oxidative deamination of lysine and hydroxylysine.
This occurs OUTSIDE the cell. - not dependent on VitC.
If no Vitamin C available what happens to the structure of collagen?
Without VitC- Lysyl hydroxylase NOT ACTIVE so can’t form hydroxylysine in the ER.
In the ECM:
Lysine is deaminated to make tropocollagen BUT
covalent bonds of lysine are WEAKer than those between hydroxylysine.
Why is hydroxylation so important to make strong collagen?
Lysine needs to be hydroxylated to form STRONGER covalent bonds when deaminated by lysyl oxidase which will form STRONGER crosslinks between the tropocollagen.
What is required for hydroxylase enzyme to be ACTIVE? What tissues most affected if not active?
Vitamin C- Scurvy
Periodontal ligament & Gingiva
- bleeding gums and loose teeth
What makes elastin so elastic? Where found?
hydrophobic monomers that are Crosslinked to each other.
ECM- blood vessels, aorta, lungs , skin
Ground substance
hydrated gel-like matrix
PG’s, Hyaluronan, glycoproteins
GAG’s
long PSchains made of disaccharide repeats.
(amino sugar–Acid sugar)
neg- attract Na+ which attracts H20 into ECM
Hyaluronin (hyaluronate)
25000 repeats- not covalent bond to proteins- neg charged- not sulfated
Chondroitin Sulfate & Dermatan sulfate
Heparan sulfate
Keratan sulfate
Short ~100 repeats
Sulfated
Covalent bond to proteins
Protein + GAG = PG (proteoglycan)
Proteoglycan structure
Core protein’s serine residue attaches to LINK TETRASACCHARIDE (xylose-galactose-galactose-glucuronic acid) that attaches to the GAG
CORE->Tetrasach>GAG
Proteoglycan agregate
Hyaluronin core–> multiple protein linked PG’s
PG-> has protein core attached to multiple GAGs
Huge hydration shell
Why are GAG’s so important to ground substance and ECM? What would happen if it was disrupted?
Water into the ECM Resist compression (cushion) Exchange Waste products- (especially important in tissues lacking vasculature) Disruption of GAG's,PGs, GS, could cause buildup of waste- toxic?
What are the proteins of the Basal lamina?
LAMININ, TYPE IV COLLAGEN, INTEGRIN. Nidogen, Perlecan, FIBRONECTIN (component of both basal lamina and CT ECM)
What is both part of BL and ECM
Fibronectin! V shaped adhering molecule with binding domains for integrins, collagen fibers, proteoglycans.
Remember picture of Two orange tubes . outside COLLAGEN tube held by V inside tube ACTIN by two blue viniculin feet and both are connected by an integrin
