Exam 1 9/11 Kingsley Flashcards
What is in the ground substance of the ECM?
glycosaminoglycans (GAGs), proteoglycans, glycoproteins, fibers
Proteoglycans are ______ covered with ____
proteins; GAGs
What are GAGs structure/components?
Structure: long, unbranched polysaccharides of repeating sugars
Components: N-acetylgalactosamine, N-acetylglucosamine; with a uronic acid
GAGs are _____ charged
negatively
What groups on GAGs make them charged?
carboxyl groups, sulfates
GAGs attract _____ and _____
cations; water
What are the four main GAG groups?
- Hyaluron
- Chondroitin
- Heparin
- Keratan
Which of the four main GAG groups is not sulfated?
Hyaluron
Sulfated GAGs are usually attached to:
proteoglycans
Hyaluronic acid size
Extremely large (100-10,000 kDa)
Hyaluronic acid attracts a large volume of:
water
Hyaluronic acid can bind ______
proteoglycans
Proteoglycans exhibit a _____ _____ configuration
bottle brush
Proteoglycans components
core protein, linked sugars (GAGs)
True or false: syndecans are roughly similar sizes
false - variety of different sizes
How are syndecans different from proteoglycans?
they are transmembrane glycoproteins; E face (usually secreted)
What is the function of glycoproteins?
large macromolecules linking cell to the ECM
Most glycoproteins have what binding domains?
GAG/proteoglycan, collagen, integrin
_____ is most abundant in connective tissue
Fibronectin
Fibronectin is a ___ linked by ____ ____
dimer; disulfide bonds
What is the amino acid sequence for fibronectin integrin binding sequence?
RGD
Glycoprotein examples
Fibronectin, laminin, hemidesmosomes, dystroglycans
What type of mutation of RGD could cause elimination adhesion and binding affinity?
deletion, point mutation, frameshift mutation, etc. Anything that could cause a change in reading frame or the protein it codes for
Deletion or mutation of RGD reduces or eliminates:
adhesion and binding affinity
What is RGD?
Integrin binding domain on fibronectin. (common feature of integrin binding domains)
Where is laminin present?
Basal and external lamina
Laminin structure
Large heterotrimer that creates a “cross”
Laminin alpha chain binds:
neurites; LG domains bind carbohydrates and integrins
Laminin beta chain binds:
each unit binds sulfated lipids, together they bind type IV collagen
Laminin gamma chain binds:
collagen, sulfated lipids
Laminin-332 can bind to:
integrin, ground substance components
a6B4 is a component of:
component of hemidesmosomes
a6B4 is a _______
integrin (receptor for laminin 5)
What are dystroglycans?
glycoproteins with two subunits
Which subunit of dystroglycan is transmembrane?
b-dystroglycan
How does dystroglycan link with cytoskeleton?
binds dystrophin in the cytosol, dystrophin binds alpha-actinin, links with cytoskeleton (F-actin)
Two major fibrous proteins
collagen and elastin
Three major categories of collagen fibers
- fibril-forming
- fibril-associated
- network forming
Collagen structure
tropocollagen helix/triple helix, glycine every 3rd aa, hydroxyproline, hydroxylysine
Collagen synthesis steps
- translation in RER
- modified in cisternae
- signal sequence removed
- proline, lysine hydroxylated
- glycosylation of hydroxyproline and hydroxylisine
- forms procollagen helix
- modified again in golgi
- secreted via trans golgi
Collagen secretion
- procollagen peptidase modifies procollagen helix
- forms tropocollagen
- tropocollagen self assembles to form collagen fibril
Unique aspect tropocollagen structure
overlaps and gaps
Which types of collagen are fibril-forming?
type 1, type 2, type 3, type 5
Which type of collagen is not fibril forming?
Type 4
Which disease is caused by deficiency/absence of Type 1 collagen?
osteogenesis imperfecta
Osteogenesis imperfecta is also known as:
brittle bone disease
What causes disruption of collagen helix in osteogenesis imperfecta?
Glycine is substituted with a bulkier amino acid, helix can’t form properly
Which disease is caused by deficiency/absence of Type IV or III collagen?
Dentinogenesis imperfecta
_____ _____ can occur in rare forms of osteogenesis imperfecta
dentinogenesis imperfecta
Dentinogenesis imperfecta symptoms
discolored teeth (blue-grey, yellow-brown); translucent teeth; weak, easily fall out or fracture
Which disease is caused by deficiency/absence of Type V (classic) or III (vascular) collagen?
Ehlers Danlos Syndrome
Ehlers Danlos Syndrome symptoms
Classic (Type V) joint hypermobility and hyperextensible skin
Vascular (Type III) problem with artery ruptures (aneurysms, often lethal
Collagen has high _____ ____
tensile strength
_____ _____ provide flexibility
Elastin fibers
Which amino acids are found in elastin?
glycine, lysine, alanine, valine, proline
True or false: like collagen, elastin also contains hydroxylysine
False
In elastin, lysine forms:
four elastin proteins bond and desmosine cross links
_____ is caused by chromosome 7 partial deletion
Williams-Beuren syndrome
Loss of elastin can cause:
supravalvular aortic stenosis
What symptom is among clinical features of Williams Beuren syndrome?
Esotropia - form of strabismus
What is observed regarding gene expression of Williams Beuren syndrome
Partial deletion of chromosome 7 which codes for elastin, so elastin cannot be produced
Basement membrane components:
- basal lamina
- lamina lucida
- lamina densa
- lamina reticularis
Components of lamina densa (basement membrane)
GAGs, proteoglycans, glycoproteins
True or false: basement membrane has very specific architecture/organization
True
Basal lamina functions
- flexible, firm support for overlying epithelium
- establishing cell polarity
- facilitating tissue differentiation
- molecular filter
Which diseases are caused by auto-antibodies?
- Epidermolysis bullosa acquisita
- pemphigus
- Pemphigoid
- Goodpasture syndrome
- Linear IgA disease
Epidermolysis bullosa acquisita (EBA) caused by:
Auto-immunity IgG develops against Type VII procollagen; leads to dermal-epidermal separation
True or false: Epidermolysis bullosa acquisita (EBA) is hereditary
False - most epidermolysis bullosa is hereditary, but EBA is not
Epidermolysis bullosa acquisita (EBA) is described as a ______ ______ disease
chronic sub-epidermal
What do Type VII collagen fibers do?
anchoring fibrils in basement membrane
Epidermolysis bullosa acquisita (EBA) is characterized by what symptoms?
spontaneous or trauma-induced blisters in areas of high contact (feet, hands, mouth); acantholysis
Pemphigus and pemphigoid are groups of:
rare autoimmune blistering diseases
What causes pemphigus?
auto=antibodies IgG form against desmoglein-3 of desmosomes
Pemphigus mostly affects:
desmosomes of stratified squamous epithelium
Pemphigoid is caused by:
auto-antibodies of IgG to BP-1 (hemidesmosome) antigen
Pemphigoid is similar in appearance to:
pemphigus except WITHOUT acantholysis
Pemphigoid is ______
cicatrial (mucous membrane) - oral
What kind of disease is goodpasture syndrome?
anti-glomerular basement membrane disease
What causes goodpasture syndrome?
autoantibodies to alpha-3 subunit of Type IV collagen (antibodies against basement membrane in lungs and kidneys)
Goodpasture syndrome may lead to:
permanent lung/kidney damage of death
How is goodpasture syndrome treated?
with immunosuppressants
True or false: goodpasture syndrome is a common disease
false - exceedingly rare
What triggers goodpasture syndrome?
lung insults such as smoke, cocaine inhalation, metal dust, organic solvents
Linear IgA (bullous) dermatitis is a _____ ___ disease
sub-epidermal bullous
Which diseases are characterized as sub-epidermal?
Linear IgA, Epidermolysis bullous acquisita, possibly pemphigus (may form bullous)
What causes Linear IgA disease?
Linear IgA deposition in basement membrane zone (BMZ); results in loss of adhesion at dermal-epidermal junction, blisters. may cause vesicles, ulcers
In Linear IgA, antibody deposition activates:
complement, neutrophils
True or false: there is only one antigenic target identified for Linear IgA disease
False - different targets (lamina lucida, lamina densa)
