Download 投影片 1

Gerald Karp
Cell and Molecular Biology
Fifth Edition
CHAPTER 7 Part 1
Interactions Between Cells
and Their Environment
Copyright © 2008 by John Wiley & Sons, Inc.
7.1 The extracellular space
• Glycocalyx (cell coat): cell-cell
interaction cell-substratum interaction
The extracellular matrix (ECM)
plays a regulatory role in determining
the shape and activities of cells
a. Collagen
b. Proteoglycans
c. Fibronectin
d. laminin
Best-defined ECM
• Basement membrane (basal lamina): a
continuous sheet 50-200 nm thick that
(1) surrounds muscle and fat cells
(2) underlies the basal surface of
epithelial tissues or the lining of the
digestive and respiratory tracts
(3) underlies the inner ECs of blood
vessels
a. Collagen (fibrous
glycoprotein)
• Found throughout in animal kingdom
• High tensile strength, that is, their
resistance to pulling forces is strong
• A collagen fiber 1 mm in diameter is
capable of suspending a weight of 10
kg without breaking.
• Is the single most abundant protein
in human body (25%)
Collagen (Cont.)
• Is produced primarily by fibroblasts,
smooth muscle cells and epithelial
cells
• More than 20 distinct types of collagen
have been identified
• All share at least two structural
features: trimers of α chains and
wound around each other to form a
rod-like triple helix
• Tendons : connect muscle and bone
• Stroma of cornea: transparency
• Type I collagen gene mutation: thin skin,
death
• Type II mutation (cartilage tissue): skeletal
deformaties
• Other mutations: hyperflexible joints,
highly extensible skin
b. Proteoglycans
(protein-polysaccharides
complex)
GAG “-” H3O ”+”
Hydrated gel
with pores
resists crushing
forces
Collagens and
GAGs give
cartilage and other
ECM strength and
resistance to
deformation.
The GAG chains also
act as binding sites
for many growth
factors, affecting
their interaction
with cell-surface
receptors
c. Fibronectin
d. Laminin
• Three different polypeptide chains
connected by S-S bonds
• Long arm and short arm
• Effect on cell migration and cell
differentiation (laminin receptor on cell
surface) i.e. guiding tips of embryoic
axons, migration of primordial germ
cell
Matrix metalloproteinases (MMPs)
• Zinc containing proteins either secreted into
the extracellular space or anchored to the
plasma membrane
• Tissue remodeling
• Migration
• Wound healing
• Angiogenesis
•
•
•
•
•
Athritis
Atherosclerosis
Hepatitis
Tooth and gum diseases
Tumor progression
7.2 Interactions of cells with
extracellular materials
• Integrins (membrane receptors)
• Focal adhesions and
hemidesmosomes: anchor cells
to their substratum
• αβ chain spans membrane, noncovalently linked, 17α,8β, 20+
kinds of integrins (Fig. 7.5)
Integrin (cont.)
•
•
•
•
Large extracellular portion
Small cytoplasmic portion
Ca2+ binding site on αchain
βchain can recognize RGD sequence on
fibronectin, activate FAK pathway
Change in conformation of the
cytoplasmic domains, increasing
the integrin’s affinity for an
extracellular ligand
• “Inside-out” theory
• The aggregation of platelets during blood
clotting occur only after the cytoplasmic
activation of αIIbβ3 integrins which
increases their affinity for fibrinogen
“Outside-in” signaling
• Integrin binds to fibronectin or collagen
• Conformational changes at the cytoplasmic
end of the integrin
• FAK
• Protein phosphorylation
• Nucleus (cell division, differentiation, motility,
growth, survival, cancer cells vs. normal
cells)
Integrins link ECM to
cytoskeletons
• Focal adhesion (in vitro with actin)
• Hemidesmosomes (in vivo with keratin,
IF)
• Out-side-in
• Normal cells (integrin dependent) and
malignant cells (integrin independent)
Bullous pemphigoid
• Individual’s bp proteins (autoantibodies) present
in these adhesive structures.
• These autoantibodies cause the lower layer of
the epidermis to lose attachment to the
underlying basement membrane.
• The leakage of fluid into the space beneath the
epidermis results in severe blistering of the skin.
• Epidermis, GI, urinary tracts
7.3 interactions of cells with
other cells
• Cells can recognize the surfaces of
other cells
• Interacting with some and ignoring
others
Little was known about the nature of
the molecules that mediate cell-cell
adhesion until
• The development of techniques for
purifying integral membrane proteins
• The isolation and cloning of genes that
encode these proteins
Four distinct families of integral
membrane proteins play a major role
in mediating cell-cell adhesion
• Cell-cell adhesion molecules
• 1. Selectins
• 2. Certain members of IgSFs and
integrins
• 3. Cadherins
• 4. Adherenes junctions and
desmosomes:
anchoring cells to other cells
1. Selectins
• LEU-CAM1 (L-selctins)
in vivo: lymphocytes homing
• A family of intergral membrane
glycoprotein
• Bind to the oligosaccharides of other
cells
• Possess a small cytoplasmic domain
and a large extracellular segment
• Role of selectins in inflammation (P.263)
2. Immunoglobulins and
integrins
• Ig domains: 70-100 amino acids
• Most IgSF mediate lymphocytes and
macrophages and target cells for immune
response
• Calcium-independent cell-cell adhesion
• Some IgSF such as VCAM, NCAM and L1
mediate interaction between nonimmune
cells i.e. nerve outgrowth, synapse
formation, nervous development
• Deformed babies due to L1 mutation,
water on the brain, mental retardation
• Integrins α4β1 binds to VCAM on blood
vessels
3. Cadherins
• Transmit signals from ECM to the
cytoplasm
• Mediate Ca2+-dependent cell-cell
adhesion
• E-cadherins, N-cadherins, P-cadherins
4. Adherins junctions and
desmosomes: anchoring cells to
other cells
• Adhesive junctions (ca2+dependent):
1.adherens junctions
2.desmosomes
3.junctional complexes (tight junction
and gap junction)