CELLS INTO TISSUE

TOPICS: - Appear to generate tissue speci c interactions

Cell to Cell Adhesion between cells
Cadherins - Plaques of classical cadherins linked to actin
Desmosomes cytoskeleton
Signaling between Cells - Form a belt that runs around the cell
Gap Junctions • Desmosomes
Extracellular matrix - linked to intermediate laments
Integrins and Signaling by Integrins - Provide increased mechanical support to cells
- Formed by desmosomal cadherins
CELL TO CELL ADHESION - Form a spot on the plasma membrane
Note: - Found in cells subjected to mechanical stress
• In order to function in tissues and organs, cells • Gap Junctions
establish contacts in form of adhesion - connect to cytoplasm of two adjacent cells
molecules - Linked to micro laments
• Extracellular matrix - provide structural, • Selectins
metabolic and growth support to cells - Ig-superfamily CAMs
- common set of bers - Promote homophilic adhesion outside of junctions
• Focal Adhesions & Hemi-desmosomes
Major Families of Cell-Adhesion Molecules
- cell-matrix junctions that are formed by integrins
(CAMS) and Adhesion Receptor
• Dimeric E-cadherins
- form homophilic (self ) cross-bridges with E-
cadherins on adjacent cells
• Immunoglobulin (Ig) superfamilies of CAMS
- form homophilic + heterophilic (non-self )
linkages
• Selectins
- dimers
- Contain carbohydrate-binding lectin domain
- Recognizes specialized sugar structures on
glycoproteins and glycolipids on adjacent cells
• Heterodimeric integrins
- function as CAMs or adhesion receptors

CADHERINS
Characteristics:
➡ Integral membrane proteins
➡ Mediate interactions between neighboring cells in
both adherens junctions and desmosomes
➡ Large family of proteins
➡ Show tissue speci c expression
➡ Contain single transmembrane domain and
variable number of extracellular cadherin
- Bind to very large, multiadhesive matrix proteins domain

Functions:
Different Complexes that Held Cells together • Surface receptors used by cells to generate contact
• Tight Junctions between each other
- build a seal between adjacent cells and are • Generate tissue-speci c interactions between cells
connected to actin laments
• Adherens Junctions
- linked to actin laments

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 Note: • Cells often change their behavior whether they are

• Cadherins interact homotypically as one family connected to other cells, and signaling via adhering
member that binds the same member junctions
• Calcium - essential for interaction between
cadherins Four Major Tansmembrane proteins of Tight
• Cadherin = calcium + adhesion Junction
• Calcium allows cadherin to extend and interact • JAMs
with another cadherin • Claudins
• Interaction between 2 cadherins is weak • Occludin
• Cadherins interact selectively with cadherins of • Cytoplasmic peripheral proteins
the same family
Transmembrane Proteins
Clustering - mediate cell-to cell adhesion
- cadherins forms clusters in one area to strengthen Cystolic TJ Complex
adherens junctions and desmosomes - connect to di erent factors that link the involved
- Achieved by linking cadherins to cytoskeleton transmembrane proteins to actin-cytoskeleton
that prevents them from di using laterally within the
membrane Regulatory Complex that maintain Integrity of TJ
• Atypical PKC (aPKC)
Interaction of Cadherins with Cadherins: • Rac1
• Cells with N-cadherin or E-cadherin will sort into • Cdc42
clusters • Par6
• High levels of cadherins cluster away from cells • Par3
with Low levels of cadherins
• Multicellular organisms use selectivity of Calcium-Dependent integrity of adherens
cadherins to separate cells with di erent fates junctions
during development - stabilized by binding of E-cadherin to
• Cadherins are linked to actin laments (in intacellular catenins
adherens junctions)

Focal Adhesions (FAs)

- structural complexes that links extracellular
matrix (ECM) to the Intracellular actin-
cytoskeleton
- Contain various integrin heterodimers
- Transmembrane receptors composed of α and β
chains
Hemidesmosomes
- located at the basal side of epithelial cells where
they link laminins to the intracellular
intermediate lament network
- Provides stable adhesion of epithelial cell layers
to the basement tissue
Alpha- and Beta Cadherin
- complex of proteins that link cadherins to actin - Consist of transmembrane proteins: :
laments
- α6β4
- Dense plaque - CD151
- BP180
Plectin
DESMOSOMES
• Use members of cadherin family to mediate cell
- mediates linkage of hemidesmosomes to the
cytokeratin network
to cell interactions
• Cluster in a spot on the plasma membrane instead
BETA-CATENIN
of a belt like adhering junctions
Desmoglein & Desmocollin Functions:
• Links cadherins to actin laments
• Functions as transcription factor
• Turns on the expression of several genes
SIGNALING BETWEEN CELLS Location:
• Adhering junctions function as signaling complexes • Adhering junctions
• Cytosol
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 Phosphorylation Interaction:
- keep low the levels of cytosolic β-catenin • Connexins interact with connexins in neighboring
Disruption of adhering junctions cells to form a continuous pore between cells.
- releases β-catenin into the cytosol
- May be insu cient to activate transcription Gap junction size may be adjust:
• Addition of more connexins (increasing the size)
Note: • Endocytosis of existing connexins (decreasing the
• S o m e s i g n a l i n g r e a c t i o n s i n h i b i t s t h e size)
phosphorylation of β-catenin, allowing it to build • Presence of calcium - reduces the pore size of
up in the cytosol and enter the nucleus to activate connexins
transcription
Note:
WNT/β-catenin signalin • Pore size of connexins is regulated
• Without WNT/β-catenin signaling • Pore size of connexins is critical during cell damage
- Destruction complex phosphorylates • Intact cells - low calcium concentrations
cystolic β-catenin - connexins are open
- Phosphorylated β-catenin is recognized and • Damage cell membrane
degraded by proteasomes - allow calcium to enter
• With WNT/β-catenin signaling - Connexins closes
- Destruction complex is inhibited to
phosphorylate cystolic β-catenin
- Unphosphorylated β-catenin accumulates
in the cytosol, translocated into the
nucleus, and activates the WNT target gene
expression

GAP JUNCTIONS
De nition: EXTRACELLULAR MATRIX
➡ Collection of pores that connects the cytoplasms of • Cells associate with a common set of extracellular
two cells bers that provide structural and metabolic
support
Pores - allow passage of small molecules Composition of Extracellular matrix:
- allow cells to relay information • Fibrous proteins
- Propagate signaling reactions throughout the tissue - Structural support
- Composition: • Proteoglycans
- Connexins - Huge protein-polysaccharide complexes
- Form a gel that varies in pore size
- Regulates the di urion of molecules
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 - Bind signaling molecules • Talin

- Regulate the extent of signaling reactions - Catalyzes the assembly of actin laments
• Hyaluronan that are linked to the integrins
- Structural support - Signaling molecule
- Made entirely of sugar residues - Recruits and activated kinases that
- Extremely long regulate di erent cellular events
- Occupies large volume
- Retains water Note:
- Resist compression • Interactions between integrins and ECM are critical
for cell growth and survival
Collagen • Most cells will not grow if not attached to the ECM
- primary brous protein • Apoptosis happens when cell migrate out of tissue
- Resist tension and lose contact with the ECM
Fibronectin & Laminin • Mutation - override anchorage dependence
- provide sites for cellular attachment - allows cells to proliferate outside proper
context
INTEGRINS
Characteristics
• Cell receptors
• Heterodimers
• Containing alpha and β-subunit
• Linked intracellular to actin laments
Functions:
• Connect cells to common extracellular bers
(extracellular matrix)
• Signaling platform for cell to regulate strength
interaction between integrins and the ECM

Note:
• There are 18 alpha genes
• There are 8 β-genes
• Di erent pairs of integrins are expressed in di erent
tissues and bind di erent components of the ECM
• Interaction between individuals integrins and ECM
is weak

• Clustering of integrins via cytoskeleton generates

more robust attachment

Signaling by Integrins
• Ligand-Binding
- Trigger the assembly of actin laments
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