Cell cell interactions.ppt

cell cell interactions

1. ExtracellularMatrix

2. Readings and Objectives
•Reading
–Cooper: Chapter 14
•Topics
•The Extracellular Matrix
•Composition
•Cell-Matrix Interactions
•Cell-CellInteractions
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3. Extracellular Matrix
Introduction
•Cell walls: bacteria, fungi, algae, and higher
plants
•Animal cell in tissues embedded in an
extracellular matrix of proteins and
polysaccharides
Function
•Provides structural support to cells and tissues
•Important role in regulating cell behavior
–Cell to cell interaction, communication
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4. General Structure of Extracellular Matrix
•Animal cells embedded in an
extracellular matrix
•Basal laminae:thin layer on which
epithelial cells rest. Also surrounds
muscle cells, adipose cells, and
peripheral nerves
•most abundant in connective
tissues
•Connective tissue
–loose connective tissue
–Bone
–tendon
–cartilage
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5. Composition of Extracellular Matrix
•Fibrous proteins
•Polysaccharides-gel like environment
•Adhesion proteins-link components of the
matrix to one another and to cells
•Different matrices have different amounts of
each component
–Tendons, rich in fibrous proteins
–Cartilage,high in polysaccharides
–Bone,calcium phosphate crystal deposition
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6. •Collagen-major structural fibrous
protein
•Forms triple helices
•Triple helix domains: repeats of the
amino acid sequence Gly-X-Y
•Glycine in every 3
rd
position
•X=Pro, packs helices closely
•Y= hydroxyproline,
synthesized in ER
•Pro, Hpro stabilizes
by helpingH-bonding
Matrix composition: Collagen
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7. •Type I collagen-the most abundant
•polypeptide chains have about 330
Gly-X-Y repeats
•Secreted through ER/golgi, form
collagen fibrils
•Triple helical molecules are
associated in regular staggered arrays
•Covalent cross-links: lysine and
hydroxylysine side chains
•strengthen the fibrils
•Fibrils form collagen fibers, several
µmin diameter
Matrix composition: Collagen
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8. •Some are not fibril forming
•Fibril-associatedcollagens: bind to
collagen fibrils, link to others or to
other matrix components
•Network-forming collagens: have
non helical interruption, cross-link
to network
•Anchoring fibrils:link basal
laminae to underlying connective
tissues
•Transmembrane collagens:
proteins that participate in cell-
matrixinteractions
Types of Collagen
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Network-forming collagens

9. •Extracellular matrix gels are polysaccharides called
glycosaminoglycans(GAGs).
•GAGs are repeating units of disaccharides: One sugar is
either N-acetylglucosamine or N-acetylgalactosamine, the
second is usually acidic (glucuronic acid or iduronic acid).
Matrix Polysaccharides
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10. •sulfate groups make GAGs
negatively charged
•bind positively charged ions
and trap water molecules to
form hydrated gel
•GAGs are linked to proteins
to form proteoglycans
Matrix Polysaccharides
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11. •Link matrix components
–to each other
–to cell surfaces
•Fibronectin: main adhesion protein
of connective tissues
•A homodimeric protein (2500
aa/subunit), binds
–collagenand GAGs
–cells
•Recognized by cell surface receptors
•Attachment of cells to the
extracellular matrix
Matrix Adhesion proteins: Fibronectin
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12. •Laminin: adehsion protein of basal
laminae
•Heterotrimeric: α, β, and γ-chains
(5, 4, 3 genes, respectively)
•have binding sites for
–cell surface receptors, eg integrins
–type IV collagen
–Proteoglycans
•Assemble to cross-linked network
•Linking cells and matrix
Matrix Adhesion proteins: Laminins
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13. Cell-Matrix Interactions
•Integrins:major cell surface
receptors, involved in attachment of
cells to the extracellular matrix
•Transmembrane proteins,
heterodimer of αand βsubunits
(18α, 8β)
•Bind to short aa in,
–Collagen
–Fibronectin
–laminin
•also anchor the cytoskeleton to the
extracellular matrix
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14. Cell-Matrix Junctions
Two types of cell-matrix junction
•Focal adhesions:bundles of
actinfilaments are anchored
to βsubunits of integrinsvia
–α-actinin
–Vinculinvia talin
•Assembly of focal adhesions
•Focal complex: small group of
integrins
•RecruiteTalin, Vinculin, α-
actininand Formin
•Formininitiates actinbundles
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15. Focal adhesions are reversible
•Integrins can reversibly bind matrix components
•change conformation between active and inactive states
•Inactive state: integrin heads turned close to cell surface
•Cell signaling extends heads to matrix
•Migrating cells: focal adhesions form at the leading edge
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16. Cell-Matrix Junctions: Hemidesmosomes
•Hemidesmosomesanchor
epithelial cells to the basal
lamina
•α6β4 integrinsbind to
lamins
•long cytoplasmictail of β
subunit binds to
intermediate filaments via
•Plectinand BP230and
BP180 (similar to
transmembranecollagens)
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17. Cell-Cell interactions
•Interactions between cells are critical for development
and function of multicellular organisms
•Cell-cell interactions:
–Transient: activation of immune cells; migration to injury site
–Stable:role in the organization of tissues.
•Cell-Cell junctions allow rapid communication between
cells
•During embryo development, cells from one tissue
specifically adhere to cells of the same tissue rather than
cells of a different tissue
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18. Cell-Cell interactions
•Cell-cell adhesion-mediated by four groups of cell
adhesion molecules
•Selectins, integrins, the immunoglobulin (Ig)superfamily,
and cadherins
•Many adhesions are divalent cation-dependent, requiring
Ca
2+
, Mg
2+
or Mn
2+
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19. Selectins
•Selectins-transient interactions betweenleukocytes and
endothelialcells
•Leukocytes slow down, flattened, migrate from the
circulation to sites of tissue inflammation
•initial adhesion
•stable adhesions
binding of integrins
to intercellular
adhesion molecules
(ICAMs) on
endothelial cells
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20. Cell to Cell Junctions
Four types of Cell-Cell connections in
animal cells
•Adherens Junctions
•Desmosomes
•Tight Junctions
•Gap Junctions
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21. AdherensJunctions
•Cadherinform stable
cell-cell connections
involve actin filaments
•Also include β-catenin,
p120, and α-catenin,
•β-catenin and p120 bind
to cadherinand help
maintain stability
•β-catenin binds α-catenin
that interacts with actin
filament of cytoskeleton
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22. Desmosomes
•link the intermediate
filamentof adjacent cells
•Desmoglein and
desmocollin
(transmembrane cadherins)
bind by heterophilic
interactions across the
junction
•Plakoglobinand plakophilin
bind to the cadherins and
link to the intermediate
filament binding protein,
desmoplakin
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23. Tight Junctions
•Tight junctions provide
minimal adhesive strength
between the cells, usually
associated with adherens
junctions and desmosomes
in a junctional complex
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24. Tight Junctions
•Tight junctionsin
epithelial cell form a
seal that prevents free
passage of molecules
and ions between
cells
•separate apical and
basolateral domains
of the plasma
membrane
•prevent free diffusion
of lipids and
membrane proteins 24

25. Tight Junctions
•transmembrane proteins, occludin,
claudin, and junctional adhesion molecule
(JAM), anchored on F-actin
•Bind similar proteins on the adjacent cell
•Sealing the space between cells
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26. Gap Junctions
•open channels through the plasma
membrane
•allowing ions and small molecules to
diffuse freely
•Proteins and nucleic acids can not
pass through
•heart muscle cells, passage of ions
through gap junctions synchronizes
the contractions of neighboring cells
•allow passage of some signaling
molecules, such as cAMP and Ca
2+
,
coordinating responses of cells in
tissues
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27. Gap Junctions
•Gap junctions are made of
transmembrane proteins
in the connexinfamily
•6 connexins form a
cylinder with an open
aqueous pore in its center,
called a connexon
•Connexonsin the plasma
membrane adjacent cells
align
•form open channels
between the two
cytoplasms
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28. Gap Junctions
•Specialized gap junctions
occur on specific nerve
cells and form an electrical
synapse
•Individual connexons can
be opened or closed
•When open, they allow
rapid passage of ions
between the two nerve
cells
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