Bme205 Chapter 7 Lecture Notes

Front 1

Glycoalyx

Back 1

- Cell coat
- Formed from carbohydrate projections from the plasma membrane
- Mediates cell-cell and cell-substratum interactions

Front 2

Extracellular matrix (ECM)

Back 2

- An organized network beyond the cell membrane
- Plays a regulatory role in determining shape and activities of the cell

Front 3

Basement membrane (basal lamina)

Back 3

- A continuous sheet which underlies epithelial tissue and surrounds blood vessels
- Helps maintain cell attachment
- Serves as a substratum for cell migration
- Forms a barrier to macromolecules

Front 4

Collagen function

Back 4

- The most abundant protein in the human body
- High tensile strength, provides insoluble framework which determines mechanical properties of ECM
- Different collagens restricted to different regions of the human body
- Serious disorders result from collagen abnormalities

Front 5

Collagen composition

Back 5

- Fibrous glycoproteins found only in the extracellular matrix
- Trimer of polypeptide chains which are wound around each other

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Collagen Type IV

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- Non-fibrillar, restricted to basal lamina
- Forms irregular, polygonal lattice

Front 7

Corneal stroma

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- Layers of collagen fibrils of uniform diameter and spacing arranged at right angles

Front 8

Proteoglycans composition

Back 8

- Protein-polysaccharide complex with a core protein attached to glycosaminoglycans (GAGs)
- Have a repeating disaccharide structure
- Negatively charged GAGs attract water and coat proteoglycans in porous, hydrated gel
- Cross-linked into large matrix by hyaluronic acid

Front 9

Proteogloycans function

Back 9

- Resist crushing forces; cushion cells
- Provide binding sites for growth hormones to protect against proteases
- Regulate diffusion of small signaling molecules in developing embryo

Front 10

Hyaluronic acid

Back 10

- Non-sulfated GAG

Front 11

Cartilage matrix proteoglycans

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- Contain about 30 keratin sulfate and 100 chrondroitin sulfate chains

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GAGs

Back 12

- Glycosaminoglycans, central molecule in proteoglycans

Front 13

Fibronectin

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- A linear, modular array of distinct polypeptides
- Each polypeptide is about 30 Fibronectin modules
- Fibronectin has binding sites for components of the extracellular matrix
- Fibronectin guides migrating cells during embyogenesis

Front 14

Laminins

Back 14

- Extracellular glycoproteins consisting of three polypeptide chains linked by disulfide bonds (cysteine-cysteine bonds)
- More than 15 types found
- Help cell migration during development
- Components of basal lamina
- Domains for interaction with proteoglycans

Front 15

Basement membrane scaffold

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- Orthogonal lattice of collagen
- Laminin molecules "weaved" into collagen lattice, connected with entactin

Front 16

Entactin

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- Protein which connects laminin to collagen matrix in basement membrane scaffold

Front 17

MMPs

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- Matrix metalloproteinases, responsible for degrading components of the extracellular matrix
- Possibly involved in tissue remodeling, embryonic cell development, wound healing, and blood vessel formation
- Regulated by TIMPs (tissue inhibitors of metalloproteinases)

Front 18

Integrin structure

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- Family of membrane proteins composed of heterodimers with alpha and beta subunits
- Can change from bent/inactive to upright/active conformation upon interaction with divalent metal ions

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Integrin function

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- Play a major role in integrating extracellular and intracellular environments
- Help cells adhere to substrata of other cells
- Binding of proteins (ligands) to integrins facilitated by tripeptide RGD

Front 20

Inside-out integrin signaling

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- Binding of Talin to cytoplasmic domain of integrin beta chains induces conformational changes
- Upright integrin can then bind to extracellular matrix ligands

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RGB peptide

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- Facilitates binding of integrins to extracellular matrix ligands
- Competitive inhibitor to fibrinogen in platelet aggregation

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Focal adhesions

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- Scattered, discrete sites for cell adhesion to their substratum in vitro
- May act as a sort of sensory structure
- Implicated in cell locomotion

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Hemidesmosomes

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- Basal attachment of epithelial cells to the basement membrane in vivo
- Contain a dense plaque of keratin filaments
- Filaments linked to the extracellular matrix by membrane-spanning integrins

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Selectins

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- Family of integral membrane glycoproteins that bind to cell surface sugars
- Contain a small cytoplasmic domain, a membrane-spanning domain, and an extracellular segment
- Three types: E-selectin (on endothelial cells), P-selectin (on platelets and on endothelial cells), L-selectin (on lymphocytes)

Front 25

Inflammatory response

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- Recruitment of lymphocytes to the site of injury
- Neutrophils attach to P- and E- selectins
- Neurophils "roll" along vessel wall
- Platelet activating factor (PAF) sends a signal to increase the binding activity of some integrins
- Activated integrins bind neutrophil to the wall of vessel

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Metastatis

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- Spread of cancer cells from tumour location to other parts of body through bloodstream
- Metastatic cells are less adhesive, are able to penetrate barriers, and are able to invade normal tissues

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IgSF

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- Immunoglobin superfamily, family of proteins, most of which are involved in immune functions
- Most IgSF proteins mediate interaction of lymphocytes with required cells
- Some members mediate adhesion between non-immune cells
- VCAM (vascular cell-adhesion molecule)
- NCAM (neural cell-adhesion molecule_
- L1 (neural development)

Front 28

Cadherins

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- Family of at least 30 related glycoproteins which mediate Ca(2+)-dependent cell-cell adhesion
- E-cadherin (epithelial), N-cadherin (neural), P-cadherin (placental)

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Function of cadherins

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- Join cells of similar types to one another by preferential binding to the same cadherin present on the neighbouring cell
- Involved in transmitting signals from the extracellular matrix to the cytoplasm
- Mediate changes in adhesive contacts during embryonic development by forming epithelial-mesenchymal transition (EMT)

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EMT

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- Epithelial-mesenchymal transition
- Loss of E-cadherin expression causes transition from tight associations to loose associations
- Involved in embryogenesis, e.g. development of the neural tube

Front 31

Adherens junctions

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- Cytoplasmic domain of cadherin molecules connected to actin filaments of the cytoskeleton by linking proteins included beta-catenin
- Cells of an adherens junction held together by calcium-dependent cadherin linkages
- Form belts near apical surface called junctional complex

Front 32

Desmosomes

Back 32

- Disk-shaped adhesive functions between cells
- Found in areas of mechanical stress, e.g. skin, gum, cervix
- Contain cadherins which link two cells across a narrow gap
- Desmosomic cadherins have desmogleins and desmocollins domain structures

Front 33

Transmembrane signaling

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- Transfer of information across plasma membrane
- Integrins and cadherins can transmit signal form the extracellular environment to the cytoplasm
- Binding of an integrin with its ligand can induce a response such as growth potential changes

Front 34

Tight junctions

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- Specialized contacts between epithelial cells
- Located at very apical end of the junctional complex between adjacent cells
- Serve as barrier to free diffusion of water and solutes from the extracellular compartment
- Some are permeable to specific ion or solutes
- Contain occludins and claudins
- Form the blood-brain barrier

Front 35

Claudins

Back 35

- Structural component of tight junctions
- May account for differences in selective permeability
- Claudin-16: expressed in kidney tubule
- Claudin-1: Claudin-1 knockout mice die from dehydration from uncontrolled water loss

Front 36

Gap junction structure

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- Sites between animal cells for intercellular communication
- Composed entirely of membrane protein connexin
- Connexins organized into a complex called connexon

Front 37

Gap function function

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- Gap junction intercellular communication allows passage of low-weight molecules
- Allow integration of activities of individual cells into a functional unit
- Connexin compatibility differences either promotes or prevents communication between different cells

Front 38

Tunneling nanotubes

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- Thin tubular process capable of carrying materials between the cytoplasms of neighbouring cells
- About 100 nm in diameter, supported by internal actin skeleton
- Can transmit viral particles and prions
- Observed in vitro