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Block Two Cell Signaling > ECM > Flashcards

ECM Flashcards

1
Q

Roles of ECM

A

Structural: network of proteins and polysaccharide chains that provides strength and organizes tissues; allows for diffusion of small molecules
- provides mechanical support
- forms barriers to keep cells in proper location
- scaffold for epithelia
- aqueous medium for nutrient and metabolite exchange
Signaling: regulates behavior of cells touching, inhabiting it, migrating through it
Influences:
- cell survival
-cell growth
- cell division
- cell differentiation
- morphogenesis (during development)

ECM also serves as resouviour for growth factors which bind to proteins and other molecules in matrix and can be released or not released as needed

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2
Q

Organization ECM

A
  • CT composed of semi-fluid gel (ground substance) w/ embedded fibers
  • Basement membranes sheet like arrangements ECM proteins underlying epithelia
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3
Q

2 main classes molecules in ECM

A
  1. Fibrous proteins- organize and strengthen matrix
  2. Glycosaminoglycan polysaccharide chains (GAGs)- form hydrating gels that resist compressive forces and allow diffusion of small molecules
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4
Q

ECM remodeling

A

ECM is not a static things; constantly remodeling via protease and protease inhibitors playing critical role in fx and dx

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5
Q

Fibrous proteins of ECM

A

Structural: Collagen, Elastin
Adhesive: Fibronectin, Lamin

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6
Q

Collagen

A

Is a superfamily, collagen I = most common; Form structure that confers tensile strength to tissues; consists of L handed triple helix w/ 3 AA per turn what wind around each other to form rope like structure; rich in glycine and proline (every third residue is glycine)

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7
Q

Assembly collagen molecules

A

Alpha chains undergo post translational modifications; selected prolines and lysines undergo hydroxylation -> intra and intermolecular cross-linkage; alpha chains self assemble in ER forming pro collagen; post secretion N and C term properties clipped off -> individual collagen molecules assembling into fibrils -> fibrils strength via cross-links btwn lysines some collagen fibrils aggregate into collagen fibers

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8
Q

Collagen post translational modifications

A

Select proline and glycine undergo hydroxylation allowing self assembly of 3 pro-alpha chains this = necessary for inter and intra molecular cross linking; Vit C= cofactor

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9
Q

Formation of collagen fibril

A
  1. Synthesis of pro alpha chain
  2. Hydroxylation of selected prolines and lysines
  3. Glycosylation of selected hydroxylysines
  4. Self assembly of 3 pro-alpha chains
  5. Pro collagen tripple helix formation
  6. secretion
  7. cleavage of propeptides
  8. Self-assembly into fibril
  9. Aggregation of collagen fibrils to form collagen fiber
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10
Q

Scurvy

A

defect in post translational modification of collagen because vit C deficiency; can -> poor wound healing, bone fractures, loose teeth, bleeding
G. Pigs and primates don’t synthesize vit C

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11
Q

Collagen Alpha chains

A

mixed and matched to make different kinds of structures; fibrillar and network forming

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12
Q

Fibrillar collagens

A

long rope like fibers; fibril associated collagens help organize the fibers

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13
Q

Network forming collagens

A

Basement membranes

Anchorning- anchor basement membranes to underlying tissue

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14
Q

Fibrillar collagen I

A

bones/ skin

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15
Q

Fibrillar collagen II

A

defining cartilage of cartilage

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16
Q

Fibrillar collagen V

A

tendon

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17
Q

fibrillar associated collagens

A

bind to surface of fibrillar collagens linking them to one another and to other components of ECM; triple stranded helices of these are interrupted by non-helical domains to confer flexibility

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18
Q

Type IV collagen

A

network forming collagen; major collagen of basement membrane; flexible structure b/c interruptions to triple helical structure, interact via uncleaved terminal domains to assemble into flexible sheet like network

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19
Q

Collagen type VII

A

anchoring collagen anchor basement membranes to underlying CT; effect in this = dystrophic epidermolysis bulls (epithelial lining peels off forming mechanical trauma)

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20
Q

Collagen and wound healing

A

Fibrilar collagens form major portion of CT at repair sites; impaired collagen synthesis interferes with wound healing

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21
Q

Fibrosis

A

excessive collagen deposits

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22
Q

Elastin

A

allows tissue to stretch and recoil
critical for arteries, lung, and skin
composed of elastin molecules covered with sheath glycoprotein microfibrils

23
Q

Elastin structure

A

composed of alternating segments of hydrophobic and alpha helical regions

  • hydrophobic segments responsible for elastic properties
  • helical segments form cross-links btwn adjacent elastin fibers
24
Q

Prevention of tissue tearing

A

elastic fibers interwoven with inelastic collagen to limit extent of stretching

25
Q

Fibronectin

A

glycoprotein
mediates cell matrix interactions contributes to organizing the matrix
most abundant ECM adhesive protein

26
Q

fibronectin structure

A

dimer composed of similar but non-identical polypeptide chains
distinct domains allow for interaction w/ other ECM constituents and PM proteins such as integrins

27
Q

Lamin

A 
fibrous protein
organizes basement membrane
organizes shape
synthesized first
has diff binding sites for diff cell surfaces; w/o lamina no BM formed at all
28
Q

Kitty with thin skin that spontaneously tears

A

biopsy showed abnormal collagen

- no hx of steroid use

29
Q

Glycosaminoglycans

A

withstand compressive forces

allow rapid diffusion of nutrients, metabolites, and hormone between blood and tissues

30
Q

glycosaminoglycan structure

A

unbranched polysaccharide chains, form hydrating gels
composed of repeating disaccharide chains that are too stiff to fold into globular units, chains = highly negative b/c sulfate or carboxyl groups on sugar = v hydrophilic = makes them resistant to compressive forces and allows rapid nutrient diffusion

31
Q

Hyaluronic acid

A

simplest glycosaminoglycan, major polysaccharide component of ECM
Present in all tissues and body fluid v important in joints as major constituent synovial fluid; allows jt to resist compressive forces
Acts as space filler facilitating cell migration during morphogenesis and tissue repair

32
Q

Hyaluronic acid structure

A

regular repeating sequence can be up to 25,000 units long; no sulfate groups; neg charge bc carboxyl group on flucouronic acid; not linked to core protein

33
Q

Proteoglycan structure

A

Glycosominoglycan; long unbranched GAG chain covalently linked to core protein; several diff core proteins and # and type of attached GAG chains variable; modification of sugar residues allows for diversity; classified by sugar (Chondrotin sulfate, keratan sulfate, dermatan sulfate, Heparan sulfate); v heterogeneous

34
Q

Proteoglycan associates

A

associated with each other, HA, fibrous proteins to form complex composits

35
Q

Proteoglycans function

A
  1. For gels act as sieves regulate passage of molecules by size and charge (for gels of varrying pore size and density)
  2. Multiple signaling roles
    - bind signaling molecules, control rate of diffusion, rate of action, and lifetime of secreted signaling molecules
    - Can also directly modify activity of these signals
    - Storage site for growth factors?
  3. Cell surface proteoglycans act as coreceptors
36
Q

Aggrecan

A

major proteoglycan of articular cartilage; 100 GAG chains attached to serine rich core protein and chondroitin sulfate and keratan sulfate chains -> hydrating gel structure -> load bearing properties and allows for diffusion of nutrients

37
Q

Osteoarthritis

A

impaired synthesis of proteoglycan components

38
Q

CKCS valve dx

A

bc too much proteoglycans (mitral valve dx)

39
Q

Basement membrane

A

specialized form of ECM formed by specific interactions among type IV collagen, laminin, nidogen, and perlecan; they underlie virtually all epithelia and form thing, though flexible sheets of proteins and polysaccharides

40
Q

Laminin structure

A

heterotrimer compost ot 3 long-polypeptdide chains held together by disulfide bonds; has diff functional domains allowing interactions w/ type IV collagen (fibrous protein), perlecan (glycosaminoglycan), nidogen(fibrous protein); self assembles through head group interaction; forms felt-like sheet

41
Q

Basement membrane function

A

underly all epithelial cells and surround some non epithelial cells
mechanical connection btwn epithelium and underlying CT
Control of epithelial growth and differentiation
primary determinants of architecture of epithelial organs
scaffold for tissue regeneration when epithelial tissues injured
serves as selective barrier to cell movement and molecular filter (glomerulus)

42
Q

Cell interaction with ECM

A

via matrix receptors especially interns and transmembrane proteoglycans

43
Q

integrin structure

A

transmembrane heterodimers consisting of alpha and beta subunits; link to cytoskeleton; large N-terminal extracelluar domain binds specific sequences of ECM proteins such as fibronectin, small cytoplasmic C-term domain connects to actin cytoskeleton via talin

44
Q

ECM and wound healing

A
  • scaffold allowing restitution of cell architecture

- spatial organization of components of neuromuscular junction

45
Q

Bladder issues what type mutation

A

Collagen Type IV

46
Q

integrein on cell membranes

A

present in higher numbers on cell membrane, bind ligands with low affinity; strong adhesions depend on clustering of multiple integrins

47
Q

integrin inactive state

A

integrein adopts tightly folded globular structure

48
Q

integrin active state

A
  • upon ligand binding intracellular domain opens up to reveal talin-binidng site allowing for linkage to cytoplasm
  • can be activated from inside-out when cytoplasmic tail binds talin extracellular domain is pushed into active conformation that can bind components of ECM
49
Q

cross talk

A

considerable cross talk between integrins and other signaling pathways

50
Q

anchorage dependence

A

most cells do not grow or proliferate unless they are attached to ECM so that cells only survive and proliferate in appropriate environments (therefore integrins influence cell survival and proliferation)

51
Q

integrin defects

A

implicated in variety of genetic dx; play role in development of cancer, autoimmune dx, and certain infectious dx

52
Q

integrins recruit

A

intracellular signaling proteins at sites of cell-substratum adhesion

53
Q

integrins vs other signaling receptors

A

Similarities: Differences:
-Cell surface receptor - structural linkage to
-Activates intracellular cytoskeleton
signaling molecules -Bind ligand with lower affinity
-higher concentration on cell
surface
-inside-out signaling

Block Two Cell Signaling (12 decks)

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