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Perio CT Biochem > ECM and Cell-Matrix interface > Flashcards

ECM and Cell-Matrix interface Flashcards

1
Q

Describe ECM.

A

a gel-like ground substance, non cellular component within all tissues and organs, consisting of:

  • fibrous proteins
  • non-fibrous glycoproteins
  • proteoglycans
  • water
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2
Q

What is a significant characteristic of ECM?

A

provides a physical scaffolding that initiates biomechanical and biochemical signals required for cellular adhesion, cell division, migration, tissue remodeling, and repair and tissue development.

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3
Q

The ECM is composed of mostly what kind of collagen?

A

type 1

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4
Q

What are all the functions of ECM?

A
  1. physical fxn: support tissues to maintain shape and flexibility
  2. biochemical fxn: controls cell growth, differentiation, tissue. remodeling, repair. inflammation, and deposition of fat.
  3. regulatory fxn: binding, integrating and controlling the presentation of growth factors and other igands to the receptor of the cells and initates signaling.
  4. Homeostatic fxn: balance between matrix deposition and its degradation by MMPs
  5. Specificity fxn: diversity and specificity of ECM composition and organization lend itself to solid structures found in bones and teeth or to a flexible structures found in cartilage and tendons.
  6. Loss of function: disruption to ECM network will result in loss of cell and tissue homeostasis and lead to diseases like cancer
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5
Q

What are the generalizations of ECM proteins?

A

ECM proteins are secreted proteins. There are two different kinds of proteins: fiber forming and non-fiber forming

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6
Q

What are examples of fiber-forming proteins? What is the function of fiber forming proteins?

A

collagen and elastins; providng structure and adhesive functions

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7
Q

What is an example of non-fiber forming proteins?

A

Laminin and fibronectin

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8
Q

What is fibronectin?

A

a glycoprotein presented as a dimer in plasma and dimer or multimeric form in ECM
- 230-270 kDa with 20 different isoforms

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9
Q

What is the function of fibronecin?

A
  • Binds cell surfaces and various compounds such as: collagen, fibrin, heparin, and actin
  • regulates cell adhesion, cell motility, wound healing, maintenance of cell shape, blood coagulation, host defense and metastasis
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10
Q

What is RGD tripeptide sequence?

A

a Arg-Gly-Asp sequence in fibronectin that is essential for collagen type 1 deposition which results in osteoblast and odontoblast mineralization.

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11
Q

How does the ECM link to the cell?

A

By the integrin-fibronectin collagen complex.
The integrin dimer is embedded in the cell membrane and is ready to bind to fibronectin . The fibronectin has the RGD code to bind to collagen.

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12
Q

What is laminin?

A

a major non-collagenous glycoprotein; a heterotrimer of 3 subunits: alpha, beta, and gamma; 15 laminin isoforms; and binds to integrin

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13
Q

What is the function of laminin?

A

cell adhesion, differentiation, migration, signaling, and homeostasis

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14
Q

List other matricellular proteins in the ECM (6)

A
  1. thrombospondin-1
  2. thrombospondin-2
  3. osteonectin
  4. osteopontin
  5. osteocalcin
  6. tenascin
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15
Q

What is the function of thrombospondin-1?

A

adhesive glycoprotein

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16
Q

What is the function of thrombospondin-2?

A

adhesive glycoprotein

17
Q

What is the function of osteonectin?

A

Regulates cell growth through interactions with the ECM abd cytokines required for collagenin bone to become calcified.

18
Q

What is the function of osteocalcin?

A

binds tightly to hydroxyapeptitie and calcium ion in bone and tooth

19
Q

What is the function of osteopontin?

A

binds tightly to hydroxyapeptitie, important for calcium ion in bone and tooth

20
Q

What is the function of tenascin?

A

migration of cell, binds to integran and syndecan

21
Q

What is an integrin?

A

a transmembrane receptors that are the bridges for cell-cell and cell-ECM interactions; crosstalk with growth factors, cytokines, and MMPs

22
Q

What are the properties of integrin?

A
  • 120-140kDa
  • a transmembrane receptor
  • essential in embryonic development and survival
  • 1/3 interact with ECM proteins through RGD
  • GFFKR sequence (gly-phe-phe-lys-arg) in the cytoplasmic tail of the alpha subunit: involved in heterodimer assembly and regulation of ligand recognition
23
Q

What happens if integrin was “knocked out?”

A

a) placental defects and embryonic hemorrhages
b) defects in epithelial adhesion to underlying basement membrame
c) bleeding disorders and defective osteoclastogenesis
d) mutation assoicated with gallbladder and breast cancer

24
Q

What are the 4 categories of ligand specificity?

A
  1. RGD receptors
  2. Laminin receptors
  3. Leukocyte-specific
  4. Collagen receptors

More than 1 integrin can bind to a specific ligand and more than 1 ligand can bind to a specific integrin

25
Q

What are the two major families of co-receptors/modifiers?

A

Syndecans

Tetraspanins

26
Q

What is a syndecan?

A

a transmembrane protein that plays an important role in ECM interactions, cooperates with integrins, binds to a variety of ligands: fibronectin and interacts with growth factors

Resuls in inducing stable adhesion through mutifunctional cell-surface co-receptors

27
Q

How does syndecan and integrin communicate?

A

crosstalk and signaling with cellular communication network factor-1

28
Q

What is tetraspani?

A

a transmembrane protein; it attenuates bone growth and enhances bone marrow adipogenesis; also can promote multiple cancer stages

29
Q

How is integrin activated?

A
  1. inside to out (intra to extracellular) - interacting with growth factors, cytokines and mediated with Talin/Kindlin
  2. outside to in (extr to intracellular) - binding to ligands
30
Q

Brief description and genetic disease of collagen 1

A
  • structural compoent of all tissues except cartilage
  • osteogenesis imperfecta: extremely fragile bone
  • autosomal dominant
31
Q

Brief description and genetic disease of collagen 2

A
  • predominant component of cartilage that mediates with proteoglycans
  • stickler syndrome type 1: facial abnormalities and joint problems
  • spondyloepiphyseal dysplasia: affects bones of the spine and the ends of long bones in arms and legs
32
Q

Brief description and genetic disease of collagen 11

A

structural component of articular cartilage and modulates cartilage matrix homeostasis;; stickler syndrome type 2

33
Q

Brief description and genetic disease of collagen 10

A
  • a non-fibrillar collagen
  • structural component of hypertrophic cartilage, regulates matrix mineralization, and compartmentalization of ECM components.
  • Schmid-type metaphyseal chondroplasia: long bones will be short and curved, widened growth plates and metaphysis
  • Osteochondritis dissecans: joint disorders in which cracks in the articular cartilage and subchondral bone in the joint
34
Q

Brief description and genetic disease of fibrillin 1

A
  • non-fibrous protein
  • major structure of microfibrills; tissue homeostasis
  • marfan syndrome: curvature of spine, aortic dilation or aneurysm
  • atherosclerosis
35
Q

Brief description and genetic disease of fibronectins

A
  • involved in cellular adhesion and ECM assembly, tissue injury, and inflammation regulation of vascular morphogenesis including angiogenesis.
  • Glomerulopathy
  • Idiopathic pulmonary fibrosis
36
Q

Brief description and genetic disease of laminins

A
  • Involved in cell adhesion, migration and differentiation

- congenital muscular dystrophy

37
Q

Brief description and genetic disease of integrins

A
  • leukocyte adhesion deficiency (LAD) : due to mutation of beta2 integrin

Perio CT Biochem (6 decks)

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