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groups of transmembrane proteins that mediate cell-cell and cell-ECM interactions

what are cell adhesion molecules?

- morphogenic movements during development
- tumor metastasis
- wound healing
- inflammation

several families of adhesion receptors have been IDed and are involved in what 4 things?

- integrins
- cadherens
- immunoglobulin superfamily
- selectins

what are the 4 groups of cell adhesion molecules (that we need to know)?

bind the CYTOSKELETON to ECM at FOCAL ADHESIONS in cultured cells

CAM TYPE #1: INTEGRINS
what do integrins do?

- tissue integrity
- organization

CAM TYPE #1: INTEGRINS
interactions of cells with ECM (and therefore integrins) is key to tissue ___ and ____

dimer (alpha-beta subunits)

CAM TYPE #1: INTEGRINS
what are integrins (structurally)?

via RGD sequence
(Arg-Gly-Asp acid)

CAM TYPE #1: INTEGRINS
how do integrins bind to ECM proteins?

no (through protein)

CAM TYPE #1: INTEGRINS

TRUE OR FALSE
integrin binds actin directly

calcium-dependent adhesion molecules

CAM TYPE #2: CADHERINS
what are cadherins (structurally)?

mediate homotypic cell-cell adhesion in the presence of calcium

CAM TYPE #2: CADHERINS
what do cadherins do?

- in a variety of tissues
- at the ZONULA ADHERENS = BELT DESMOSOMES in intestinal epithelial cells

CAM TYPE #2: CADHERINS
where are cadherins found?

catenins

CAM TYPE #2: CADHERINS
interaction with SPECTRIN- and ANKYIN-LIKE proteins (the ____) associated with ACTIN filaments at adherent junctions (BELT DESMOSOMES)

because EC segments of CAMs fold into 2-6 Ig-like domains

CAM TYPE #3: IG SUPERFAMILY
why are Ig-superfamily of proteins named as such?

- TCRs
- IGs
- MCH I and MCH II
- CD4 and CD8 (in picture?)
- NCAMs (in picture?)

CAM TYPE #3: IG SUPERFAMILY
what are some example of Ig superfamily CAMs?

(is that what this slide is saying?)

- identical

trans-homophilic
trans-heterophilic

CAM TYPE #3: IG SUPERFAMILY
Ig superfamily molecules on one cell can bind to ____ molecules on another cell

what is this called?

ICAM and VCAM

CAM TYPE #3: IG SUPERFAMILY
what 2 molecules play an important role in T-CELL interactions and binding of LEUKOCYTES to activated or resting ENDOTHELIAL cells?

- a CHO recognition domain (CRD) specific for a particular SUGAR

- domain homologous to a repeat found in EGF

- many consensus repeats found in complement regulatory proteins

CAM TYPE #4: SELECTINS
selectins have 3 domains. what are they?

- L selectins
- E selectins
- P selectins

CAM TYPE #4: SELECTINS
what are the 3 major types of selectins?

- carried by lymphocytes
- bind to SULFATED CHOs

CAM TYPE #4: SELECTINS
who carries L selectins?
what do they have a binding affinity for?

activated endothelial cells

CAM TYPE #4: SELECTINS
who expresses E selectins?

platelets and activated endothelial cells

CAM TYPE #4: SELECTINS
who expresses P selectins?

- integrins
- ICAMs

called honing

CAM TYPE #4: SELECTINS
selectins, together with ___ and ____ molecules, play a significant role in INFlAMMATION and in the periodic MIGRATION OF LYMPHOCYTES from the circulation into lymphoid organs. What is this called?

- selectin phase
- integrin phase

what are the 2 phases of honing?

1) neutrophils resist shear forces to slow down

2) selectins on endothelial bind to CHO on neutrophil

3) integrin receptors for ICAM1 and ICAM2 are activated, strengthening bond

4) transendothelial migration

what are the steps of honing?

- shear forces
- rolling

which steps of honing take place during the selectin phase?

- strengthening of leukocyte-endothelial cell bond
- transendothelial migration

which steps of homin take place during the integrin phase?

High Endothelial Venules (HEVs)

what allows for the transition of lymphocytes from the blood stream to the lymph tissues?

- deep cortex
- medulla
of lymph nodes

where are HEVs located?

lymphocyte (L) is squeezing its way through the junctino of 2 endothelial cells

what is going on in this picture?

- occluding junctions
- zonula adherens
(belt desmosomes)
- macula adherens
(spot desmosomes)
- hemidesmosomes

what are the 4 types of anchoring junctions?

OCCLUDING JUNCTIONS
- define cell POLARITY
- control passage of substances between ADJACENT cells
- have BELTlike appearance

ZONULA OCCLUDENS
(OCCLUDING JUNCTIONS)
- define cell _____
- control passage of substances between ____ cells
- have ____like appearance

ZONULA ADHERENS
(BELT DESMOSOMES)
- have BELTlike distribution
- a/w ACTIN filaments

ZONULA ADHERENS
(BELT DESMOSOMES)
- have ____like distribution
- a/w ____ filaments

MACULA ADHERENS
(SPOT DESMOSOMES)
- have SPOTlike distribution
- a/w INTERMEDIATE filaments

MACULA ADHERENS
(SPOT DESMOSOMES)
- have ____like distribution
- a/w ____ filaments

HEMIDESMOSOMES
- link the basal domain of an epithelial cell to the BASAL LAMINA
- intermediate filaments are a/w a PLAQUE

HEMIDESMOSOMES
- link the basal domain of an epithelial cell to the ______
- intermediate filaments are a/w ____

communicating/gap junction

which type of junction is involved in COMMUNICATION?

lateral

zonula occludens,
zonula adherens,
macula adherens,
and gap junctions are arranged along the ____ surfaces of columnar epithelial cells from the APICAL end to the BASAL lateral end

zonula occludens (tight/occluding junctions)

which type of junction is a SELECTIVE PERMEABILITY BARRIER?

epithelial cells
- capillaries
- BBB
- hepatocytes (bile canaliculi)

JUNCTION TYPE #1: OCCLUDING JUNCTIONS

tight/occluding junctions are only found in ___ cells

(and specifically what 3 tissues?)

- occluden
- claudin
(integral membrane proteins that create the intracellular barrier)

JUNCTION TYPE #1: OCCLUDING JUNCTIONS
what are occluding junctions made from?

ZO1,2,3-protein complex

JUNCTION TYPE #1: OCCLUDING JUNCTIONS
what is the name of the complex at the intracellular domain of claudin?

tight junctino between lateral surfaces of hepatocytes to prevent leakage of bile into the ECM

identify the arrowhead

- zonula adherens (belt desmosome)
- macula adherens (spot desmosome)

which type of junctions are involved in CELL TO CELL ATTACHMENTS?

cadherin

JUNCTION TYPE #2: ZONULA ADHERENS (BELT DESMOSOME)
what CAM is found in zonula adherens?

actin

JUNCTION TYPE #2: ZONULA ADHERENS (BELT DESMOSOME)
cadherin attaches to ___ filaments and forms contractile belt around the cell

terminal web

JUNCTION TYPE #2: ZONULA ADHERENS (BELT DESMOSOME)
zonula adherens are part of the _____ at the apex of columnar epithelium

belt desmosomes

JUNCTION TYPE #3: MACULA ADHERENS (SPOT DESMOSOME)
found just below ____ in stratified squamous and muscle cells

desmogleins

JUNCTION TYPE #3: MACULA ADHERENS (SPOT DESMOSOME)

which adhesion protein is found in spot desmosomes, related to cadherins?

desmoplakins

JUNCTION TYPE #3: MACULA ADHERENS (SPOT DESMOSOME)

which adhesion protein is the attachment sites for intermediate filaments, carboxy-terminal cytosolic domain?

epidermis and dermis
- stratified squamous
- stratum spinosum (2)

in the upper image, ID
- tissue
- layer 2

STRATUM SPINOSUM

AH = spots where cells are tightly attached (spot? desmosomes)

in the lower image, identify
- layer
- arrowheads

BM, intermediate filaments

JUNCTION TYPE #4: HEMIDESMOSOMES
are attached to the ___ and to
_____ intracellularly

- A6B4 integrin
- bullus pemphigoid antigens (collagen XVII)

JUNCTION TYPE #4: HEMIDESMOSOMES
have what 2 anchoring proteins?

blistering diseases

JUNCTION TYPE #4: HEMIDESMOSOMES
what diseases affect hemidesmosomes?

all layers of epidermis

JUNCTION TYPE #4: HEMIDESMOSOMES
which layers of the epidermis is desmoglein 1 present in?

basal
spinous

JUNCTION TYPE #4: HEMIDESMOSOMES
which layers of the epidermis is desmoglein 3 present in?

an autoantibody-mediated blistering disease in which antibodies against DESMOGLEIN1 cause a loss of adhesion of KERATINOCYTES in the superficial layers of the epidermis

JUNCTION TYPE #4: HEMIDESMOSOMES
what is pemphigus follaceus?

glycoproteins

JUNCTION TYPE #4: HEMIDESMOSOMES
the differentiation of splitting of the epidermis is thus related to the distribution isoforms of the ___

upper

JUNCTION TYPE #4: HEMIDESMOSOMES
in pemphigus foliaceus, the epidermis is split in its ____ region

basal

JUNCTION TYPE #4: HEMIDESMOSOMES
in pemphigous vulgaris, the epidermis is split immediately above the ____ layer of cells

pemphigous

JUNCTION TYPE #4: HEMIDESMOSOMES
identify the disease

small molecules

JUNCTION TYPE #5: GAP JUNCTIONS
signals are transmitted from 1 cell to the next by intercellular passage of ___

- cardiac
- smooth muscle
- epithelium

JUNCTION TYPE #5: GAP JUNCTIONS
where are gap junctions abundant?

connexin

JUNCTION TYPE #5: GAP JUNCTIONS
what protein forms hexagonal cylinders between cells in gap junctions?

gap junction (part of intercalated disc of CARDIAC muscle)

identify the top picture arrow

gap junctions between 2 SMOOTH MUSCLE cells

identify the bottom picture arrow

...

summary of cell junctions

- water
- ions
- structural proteins
- glycosaminoglycans
- proteoglycans
- adhesive protens

what are the 6 components of ECM?

(not sure we need to know this from here on out)

- collagen (strength)
- elastin (resilience)

what are the 2 structural proteins in ECM?

what features do they give it?

proteins with attached glycosaminoglycans

what are proteoglycans?

- fibronectin
- laminin
- nidogen

what are the 3 types of adhesive proteins?

fibronectin

which adhesive protein
- exists in 2 forms
soluble
insoluble
- is modular (can mediate binding of ECM molecules to integrin, e.g.)

soluble

which type of fibronectin is involved in wound healing?

insoluble

which type of fibronectin is involved in being secreted and surrounding fibroblasts to increase adhesiveness and therefore decrease cancer?

laminin

which adhesive protein
- has 3 subunits (alpha beta1beta2)
- has 2 types

laminin 1

which type of laminin is in the
LAMINA DENSA and mediates interaction between cell surfaces and BMs

laminin 5

which type of laminin is in the LAMINA LUCIDA and is located in anchoring filaments?

nidogen

which adhesive protein has a dumbbell shape and is between LAMININ1 and TYPE IV COLLAGEN?

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