AC Lecture 38-39: Intercellular architecture Flashcards
List the different types of cell adhesion molecules (CAMs).
cadherins
the Ig superfamily
integrins
selectins
How are CAMs used?
regulate cell migration, proliferation, and cell death
What are CAMs?
molecules that maintain adhesion between cells and other cells as well as between cells and their extra cellular matrix
What are the characteristics of cadherins?
homophelic
Ca2+ binding
bind actins and IF
What are the characteristics of integrins?
connect cells to extracellular matrix (heterophilic binding)
bind actins (except for alpha6beta4 interacts with IFs at hemidesmosomes)
cell matrix receptors that require Ca2+ or Mg2+ for ligand binding
What are the characteristics of selectins?
mediate Ca2+ dependent cell:cell adhesion in the bloodstream
mostly on immune cells
help cells find their way out of the blood stream
What are the functions of the ECM?
hold tissues together
provide cushioning (cartilage) and strength (tendons)
act as a reservoir for growth factors
Why do epithelial cells have a polarized cell organization?
divide different body cavities
provide barriers between the gut and the blood and the blood brain barrier
different functions (absorption of nutrients on one membrane and their secretion from another)
List the kinds of epithelial cells.
simple columnar (mucus secreting) simple squamous (found lining blood vessels) transitional (found in cavities subject to expansion such as bladder) stratified squamous (found in mouth and vagina linings acts to resist abrasion)
How do we describe the orientation of membranes?
apical (outer facing; typically have large surface area and villi)
lateral and basal (separated from the apical via specialized cell junctions)
What is “inside-out” signaling?
where intracellular events promote interactions between the cell and the ECM
What is “outside-in” signaling?
extracellular events (such as ligand binding) that cause interactions between the cell and the ECM
List the kinds of cell junctions in epithelial cells.
Tight junctions
anchoring junctions (adherens junctions
desmosomes)
What are tight junctions?
(occluding junctions)
seal epithelial cells together in sheets
prevents passage of small molecules between cells (allow for separation of body cavities)
separate the apical and basolateral surfaces
What are anchoring junctions?
join cells to each other and to ECM
can be adherens junctions or desmosomes
What are adherens junctions and desmosomes?
hold cells together and are formed by focal adhesions and hemidesmosomes (bind cells to ECM)
How do the two kinds of junctions differ?
types of protein that perform the anchoring functions and the cytoskeletal filament types that attach on the inside of the cell
focal adhesions: integrin proteins bind to ECM and attach to actin inside the cell
hemidesmosomes: intermediate filaments bind inside the cell
What are cadherins?
large glycoproteins that link by a homophilic mechanism
linc to actin cytoskeleton via catenins (adapter proteins)
What mediates integrin’s interaction with actin?
anchor proteins (e.g. talin, alpha-actin, and filamin)
What proteins are found in tight junctions?
claudins
occludins
What are communicating (gap) junctions?
clusters of pores found in virtually every cell in the body composed of connexins
used for amplification of a response across a tissue from a local source (e.g. neuromuscular junction)
List diseases caused by mutation in connexin genes.
sensorineural hearing loss (GBJ2 gene)
demyelinating disease (CMT)
skin diseases and arythmias
congenital cataracts
What is the ECM?
a mixture of proteins and polysaccharides
abundant in bone and cartilage (low amounts in brain and spinal cord)
How is the ECM produced?
by cells such as fibroblasts in the local matrix (can be specialized for different kinds of ECM such as osteoblasts that make bone)
What are the main components of the ECM?
collagens
proteoglycans
multi-adhesive connectors (e.g. fibronectin and laminin)
What is the basal lamina?
flexible mats of specialized matrix that underlies epithelial cell sheets and tubes
separates cells from surrounding connective tissue and serves as a highly selective filter
What are the components of the basal lamina?
laminins
Type IV collagen
Perlecan
Nidogen
What are laminins?
large cross shaped proteins containing three chains
bind each other via N-terminal globular domains to form mesh-like network
help cells interact with ECM
main ligand for integrins in hemidesmosomes
What is Type IV collagen?
forms a 2D lattice on the underside of the basil lamina towards the connective tissue
triple helical structure with N and C terminus
What is perlecan?
form of proteoglycan
contains a core polypeptide attached to large number of carbohydrate chains of glycosaminoglycans (GAGs)
integrates nidogen
What is nidogen?
protein that crosslinks all other compounds together including the other components of the basil lamina
How does connective tissue differ from solid tissues?
connective tissue (e.g. tendons and cartilage) are mostly ECM rather than cells
What is the composition/arrangement of tendons?
Collagen I (packed together in microfibrils) are packed into fibrils which are packed into collagen fibers these collagen fibers are then offset/staggered to give the striated appearance and are crosslinked to stabilize the side by side packing
What can be caused by mutation in Type I collagen?
osteogenesis imperfecta
What is the composition/arrangement of cartilage?
Type II collagen in a mesh framework
What are proteoglycans?
formations of carbohydrates and proteins that form the basis of higher order ECM structures
GAG chains bind water and provide hydration to resist compressive forces
Where are proteoglycans found?
abundant in cartilage and neural ECM
What is fibronectin?
a large, multi-domain glycoprotein that assembles outside of cells into fibrillar structures and interacts with integrins as well as other extracellular matrix proteins (e.g. collagen, fibrin, and heparan sulfate proteoglycans)
What is elastin?
fibers that allow for recoil after transient stretch
sheathed by microfibrils containing fibrillin
rich in glycine, proline, and hydroxyproline
What happens when there are mutations in fibrillin?
Marfan syndrome (leads to defects in tissues rich in elastin fibers such as the aorta which is prone to rupture in extreme cases)
Describe DMD.
Duchenne Muscular Dystrophy is caused by mutations to dystrophin (DMD gene)
part of a complex that connects the ECM to actin inside muscle cells (dystrophin glycoprotein complex) to help stabilize the muscle cells and integrate signal pathways
What are different forms of selectin?
L-selectin: found in white blood cells
P-selectin: found in platelets
E-selectin: expressed by endothelial cells; binds carbohydrates on white blood cells and platelets during inflammation
What proteases help remodel the ECM?
matrix metalloproteases (MMPs)
adamlysins
merpins
other proteinases (e.g. urokinase and tissue plasminogen activator)
What are MMPs?
matrix metalloproteases
secreted as zymogens and activated by other proteases or by thiol oxidation
can degrade all components of the ECM
natural inhibitors exist to regulate activity
What are ADAMS?
adamlysins
sheddases that cleave the extracellular domains of cytokines and growth factor receptors
What are Merphins?
involved in collagen cleavage
not well understood
