Beyond the cell: Extracellular Structures, Cell Adhesions, and Cell Junctions

1
Chapter 17

• Beyond the cell Extracellular Structures, Cell
  Adhesions, and Cell Junctions

2
Extracellular structures

• Structure that is external to the plasma membrane
• Produced by cells and then secreted
• Animals
• Extracellular matrix
• Division, motility, differentiation, adhesion
• Plants, fungi, algae, prokaryotes
• Cell wall
• Rigidity, permeability barrier, protection

3
CELL WALL
4
Cell wall composition ---Cellulose
(beta-D-gluocse) ---Hemicellulose( Glucose,
Galactose,mannose) --Pectins ( galactouronic
acid) --Extensins (protein-polysacharides
complex) --Lignins ( aromatic alcohols)
5
Extracellular Matrix (ECM)

• Structural proteins strength flexibility
• Collagens
• Elastins
• Protein-polysaccharide complexes matrix for
  structural proteins
• Proteoglycans
• Adhesive glycoproteins attach cell to matrix
• Fibronectins
• Laminins

6
Extracellular Matrix - examples
Bone rigid extracellular matrix
Fig. 17-1
7
Extracellular Matrix - examples
Cartilage flexible matrix Large amounts of
proteoglycans
Fig. 17-1
8
Extracellular Matrix (ECM) - examples
Connective tissue (gel-like structure) gelatano
us ECM large numbers of collagen
Fig. 17-1
9
Extracellular Matrix (ECM)

• Structural proteins strength flexibility
• Collagens
• Elastins

10
Collagen

• Collagen proteins form fibers with high tensile
  strength
• Tendons and ligaments
• Provides strength to ECM
• Most abundant protein in vertebrates (20 of
  total body)
• Secreted by connective-tissue cells such as
  fibroblasts

11
Collagen

• Rigid triple helix
• High in glycine, hydroxylsine, hydroxylproline

Fig. 17-2
12
Collagen assembly
Figure 17-3
13
Collagen assembly

• Synthesized in ER lumen as procollagen
• Alpha chains assemble into triple helix
• Procollagen secreted into intercellular space
• Cleaved by procollagen peptidase
• Collagen molecules assemble into collagen fibrils
• (Inter-molecules interactions by hydrogen bonds)
• Fibrils assemble into collagen fiber

14
Collagen

• 25 genes encoding collagen alpha chains
• Different combinations form at least 15 types of
  collagen
• Collagens are tissue specific

15
Elastins

• Elasticity and flexibility
• Can stretch several times their length
• Lung tissues, arteries, skin intestines
• Glycine proline
• Cross-linked by covalent bonds between lysines
• Aging collagens more crosslinked, elastins lost
• Less flexible bones and joints, wrinkled skin

16
Elastins
Fig. 17-4
17
Extracellular Matrix (ECM)

• Protein-polysaccharide complexes matrix for
  structural proteins
• Proteoglycans

Glycoproteins attached to glycosaminoglycans
(GAG)
18
Glycosaminoglycans

• ----Repeating disaccharide
• Amino sugar Sugar or sugar acid
• Amino sugar
• GlcNac, N-acetylgalactosamine
• Usually has attached sulfate group
• Sugar/sugar acid
• galactose, glucoronate (glucuronic acid)
• ----Hydrophilic negative sulfate carbohydrate
  groups
• Attracts water cations.

19
Glycosaminoglycans

• Most common
• Chondrotoin sulafate, keratan sulfate,
  hyaluronate
• Most bound to core proteins (1-200 GAGs/protein)
  ?
• proteoglycan

20
Proteoglycans

• Can be single or attached to long hyaluronate
• molecules

Fig.17-5
21
Proteoglycans
1-Hydrophilic --- absorb water extracellular
sponges resistant to physical
force 2-Lubricant --- hyaluronate can exist
as free GAG lubricating properties in joints
22
Proteoglycans
3-Anchor cells to ECM May be 1-Integral
membrane components 2-linked covalently to
membrane phospholipids 3-bind to specific
receptor proteins on outer plasma membrane
23
Adhesive Glycoproteins
Reinforce links between ECM and plasma
membrane ---Fibronectins ---Laminins
24
Fibronectins
Family of closely related glycoproteins Bind
cells to ECM, guide cellular movement Soluble in
body fluids Insoluble in ECM Partially soluble
at the cell surface Posttranscriptional
processing of mRNA (one gene-------several mRNA)
25
Linker
Arginine-glycine-Aspartate
Fig. 17-6
26
Fibronectins
Extracellular fibronectin intracellular actin
Fig 17-7
27
Fibronectins
Cellular movement e.g. embryonic cells
migrating to destination Cancer cells lack
fibronectin leading to loss in cell shape and ECM
detachment Plasma fibronectin soluble form in
blood clotting binds fibrin
28
Laminins
Found in basal lamina thin sheet of specialized
extracellular material separates epithelial
cells from connective tissue surrounds
muscle, fat and Schwann cells structural
support, permeability ---type IV
collagen ---proteoglycans ---laminins ---
entactin
Connective tissue cells cannot enter epithelial
layer White blood cells can
29
(No Transcript)
30
Integrins (linker)
Cell surface receptors that bind the ECM Bind
collagen, fibronectin laminin
31
Integrins
2 large transmembrane polypeptides
Noncovalent Differ in subunit size and binding
specificity (alpha) Some bind RGD sequence of
glycoprotein Cytoplasmic side binding sites
for specific cytoskeletal molecules
Fig. 17-10
32
Interactions between integrins the cytoskeleton
Focal adhesions Hemidesmosome
33
Interactions between integrins the cytoskeleton
Focal adhesions localized points of
attachment between cell surface integrins and
the extracellular matrix integrin molecules
clustered several linker proteins bundles
of actin microfilaments
34
Interactions between integrins the cytoskeleton
Fig. 17-11
35
Interactions between integrins the cytoskeleton
Hemidesmosomes point of attachment between
cell surface integrin molecules of epithelial
cells and the basal lamina Integrin molecules
anchored via linker proteins to intermediate
filaments of the cytoskeleton
36
Interactions between integrins the cytoskeleton
Fig. 17-11
Linker proteins form a plaque Plakin family
proteins are prominent
37
Integrins
Regulate cell movement Regulate cell
attachment Interact with intracellular signaling
pathways e.g. MAPK activations causes integrin
clustering Can activate intracellular signaling
pathways Anchorage-dependent growth Cells must
be attached to a substratum to grow otherwise
apoptosis occurs integrin clustering recruits
kinases (e.g. F(focal)AK) to focal adhesions
via adapter proteins (e.g. paxillin) Cancer
cells anchorage independent growth contain
constitutively activated FAK
38
Cell-Cell Recognition Adhesion
39
Cell-Cell Recognition
Transmembrane proteins
Homophilic interaction
Heterophilic interaction
Fig. 17-12
40
Cell-Cell Recognition
N-CAM (neural cell adhesion molecule) IgSF
member (immunoglobulin superfamily) Cadherins-
similar to N-CAMs, but require calcium
Homophilic interaction
Heterophilic interaction
Fig. 17-12
41
Cell-Cell Recognition
Cadherins- Similar to N-CAMs, but require
calcium Extracellular domain - structurally
similar repeats Vary in repeat cytosolic
domain E-cadherin 5 repeats Tissue specific
expression ---Important in embryo
development ---Cancer cells that metastasize
lose cadherin
Fig. 17-13
42
Cell-Cell Recognition
Cadherins-
Fig. 17-14
43
Cell-Cell Recognition
Cadherins-
Fig. 17-15
Normal blastula
EP-cadherin-
44
Cell-Cell Recognition - importance of
carbohydrates
CAM and Cadherin carbohydrate side chains ?
strength specificity of cell-cell
interactions N-CAM long repeats of
sialic acid Carbohydrate binding proteins
secreted by animals and plants lectins ABO
blood group Selectins leukocyte adhesion
45
(No Transcript)
46
(No Transcript)
47
ABO blood group
Glycolipids (antigen) on the red blood cell
surface
O
Universal donor
No sugars
A
B
N-acetylglucosamine
Galactose
AB
N-acetylglucosamine
Universal acceptor
Galactose
Does not contain anti- A and B antidodies
48
Cell Junctions
Long term associations between cells Animal adhe
sive junctions (anchoring junctions) tight
junctions gap junctions Plant Cell wall
plasmodesmata
49
Adhesive Junctions
Link cytoskeleton of one cell to that of
neighboring cells or ECM Distinct types of
proteins intracellular attachment proteins
junction intracellular cytoskeletal
filaments cadherins bind cells to each
other Two types of structures Adherens
junctions Desmosomes plaque formed by
intracellular attachment proteins
50
Adherens Junctions
Space between adjoining cells 20-25 nm Prominent
in heart muscle and epithelial cells (line body
cavity, cover organs) Form an adhesion belt in
epithelial cells Form smaller points of
attachment in non-epithelial cells (e.g.
neurons) b-catenin binds cytosolic tail of
cadherin recruits a-catenin ? Actin
51
Adherens Junctions
Fig. 17-17
52
Desmosomes
Fig. 17-18
Intermediate filaments
Cadherins interact with plaque at inner
membrane surface, mediate cell-cell adhesion at
the outer membrane surface
plakoglobin - b-catenin family Desmoplakin -
plakin
Desmosome core
53
Cell Junctions
Long term associations between cells Animal adhe
sive junctions (anchoring junctions) tight
junctions gap junctions Plant Cell wall
plasmodesmata
54
Tight junction
No space in between cells Molecules must pass
through cells Act as gates-fluids, ions,
molecules fences block lateral membrane lipid
protein movement membrane
polarization Intestinal epithelial cells Ducts
cavities of glands Urinary bladder (prevent
seepage of urine)
Fig. 17-12
55
Tight junction
Connected by ridges
Fig. 17-19
56
Gap junction
Cells separated by 2-3 nm gap Cytoplasmic
contact between cells Ions and small molecules
can pass through gap junction Electrical and
chemical (monosaccharides, amino acids,
nucleotides) Communication Abundant in nerve and
muscle tissue heart tissue (current that causes
heartbeat) brain (cerebellum rapid muscular
activities)
57
Gap junction - structure
Hollow cylinders
Vertebrates-composed of connexin
protein Invertebrates innexin proteins
58
Cell Junction Summary
59
Animal vs. Plant