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ECM Flashcards

1
Q

Collagen characteristics

A

TRIPLE HELIX of ALPHA-chains

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2
Q

Collagen fn

A

Provides TENSILE STRENGTH

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3
Q

What is collagen made by?

A

Fibroblast

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4
Q

What AA is in a collagen?

A

GLYCINE (@ every 3rd AA!!!)
Proline (& hydroxyproline)
Lysine (& hydroxylysine)

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5
Q

What does proline and hydroxyproline offer to the collage?

A

KINKS

Helps helix formation

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6
Q

Collagen synthesis brief steps

A

1) Pre-procollagen → procollagen after ER sig seq trimmed in rER
2) HYDROXYLATION
3) GLYCOLSYLATION
4) DISULFID formation → aligns & initiates TRIPLE HELIX FORMATION (zipper)

5) secreted and both terminus trimmed → now it is COLLAGEN FIBRIL

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7
Q

What is the purpose of procollagen?

A

prevents premature fibril formation

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8
Q

What is the purpose of hydroxylation in collagen

A

↑ stability

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9
Q

Lack of vit c / asocrbic acid =

A

Less hydroxylation =

↓ stability of TRIPLE HELIX

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10
Q

↓ vit c = ____

A

No hydroxylation

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11
Q

What needs to be done to go from procollagen → collagen?

A

PEPTIDASE trim N & C propeptides

Then SELF ASSEMBLY into collagen FIBRILS

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12
Q

What bond holds together procollagen triple helix?

A

H bonds

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13
Q

What does lysyl oxidase do?

A

DEAMINATES lysines & hydroxylysines

Deamination → makes aldehydes

Needed 4 cross linking

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14
Q

Fibrillar collagen

A

Types 1, 2, 3, 5

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15
Q

FACIT collagen

A

Type 6, 9 & 12

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16
Q

Sheet/network forming collagen

A 
Type 4 (BASAL LAMINA)
And 10
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17
Q

Anchoring fibril =

A

Type 7 collagen

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18
Q

Ehrers danlos syndrome defect

A

Defect in fibrillar collagen synth

Leads to having only elastin

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19
Q

Fn of FACITs

A

Organize fibrils in the ECM

Bid 2 surface of fibrillar collagen

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20
Q

Fn of MMPs

A

Break up ECM collagen (4 diapedesis) aka collagenases

ZiNC dependent E’s

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21
Q

What do MMPs need to fn?

A

ZINC

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22
Q

2 components of ECM

A

Fibrous P’s (collagen & elastin)

& Ground Substance (GAGs, Proteoglycans, laminin, fibronectin…)

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23
Q

What is abundant in elastin?

A

Rich in PROLINE & GLYCINE

But NOT glycosylated & NO HYDROXYLYSINE

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24
Q

What is a fibrillin gene mutation?

A

MARFANS

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25
What binds to elastin and what is its role?
FIBRILLIN Fn = essential 4 ASSEMBLY & integrity of elastic fibers
26
Marfans
Fibrillin mutation | Aortic root
27
COPD
↓ alpha-1 AT
28
What does smoke do to effect COPD
Smoke = INHIBITOR OF a1-AT
29
What do GAGs do?
Covalently link to core protein (except HYLAURONAN) to form PROTEOGLYCAN?
30
What is unique about hyaluronan
Does NOT bind to core protein Rpting seq of Identical NONSULFATED disacch's Made in WOUND HEALING Joint LUBRICANT BACKBONE for large proteoglycan complexes
31
HYALURONAN
``` NOT CORE PROTEIN BOUND WOUND HEALING JNT LUBE NONSULFATED BACKBONE ```
32
LARGE proteoglycan complex with hyaluronan = ___
Aggrecan
33
Hyaluronic Acid (IS/IS NOT) COVALENTLY bound to proteins
IS NOT
34
4 parts of ECM =
Type 4 collagen Laminin Entactin/nidogen Hspg (perlecan)
35
What type of collagen can be found in the basal lamina
4
36
Laminin role
Forms SCAFFOLD with collagen type 4 ORGANIZES assembly of basal lamina by binding to integrins and dystroglycans
37
What is the role of PERLECAN & SYNDECAN?
Bind & RECRUIT GFs
38
Hspg perlecan
Rich in basal lamina of KIDNEY GLOMERULUS
39
Mmp
Zinc
40
Vit c
Hydroxylation
41
Interstitial matrix vs basal lamina
Interstitial matrix = SPACE btw epi & endo thelium BL = UNDER EPITHELIUM
42
General role of FIBRONECTIN
Connects cells to all ECMs | Except type 4 -- BL
43
Fibronectin connects to what? At what part of the fibronectin?
Fibronectin BINDS 2 INTEGRIN @ RDG SEQ of the fibronectin
44
Fns of fibronectin
STABILIZE CELL ADHESION TO ECM Cell migration WOUND HEALING
45
2 things that bind to integrins
Fibronectin & laminin
46
Integrin
Principal cell R's for binding ECM
47
2 types of integrin anchoring jxns
``` Focal adhesions (motility) Hemidesmosomes (strength) ```
48
Hemidesmosomes PARTS
IF (keratin) - PLECTIN - INTEGRIN - LAMININ - COLLAGEN 7
49
FOCAL ADHESION PARTS
ACTIN - VINCULIN&TALIN - INTEGRIN - FIBRONECTIN
50
FOCAL ADHESION
MOTILITY
51
FAK
FOCAL ADHESION KINASE Integrins signal thru FAK 2 regulate Rho GTPase
52
Bullous pemphigoin
HEMIdesmosome
53
``` Focal adhesion (fn) PARTS ```
``` Fn = motility F-ACTIN VINCULIN&TALIN INTEGRIN FIBRONECTIN ```
54
HEMIDESMOSOME (fn) | PARTS
``` FN = STABILITY IFs (KERATIN) PLECTIN INTEGRIN LAMININ COLLAGEN 7 ```
55
PLECTIN
HEMIDESMOSOME ADAPTER P
56
VINCULIN & TALIN
FOCAL ADHESION ADAPTER P | Mn: 2 words = 2 adaper P's
57
G proteins 4 cell motility
RAC (lamellipodia) Cdc42 (filopodia)
58
Cdc42
Filopodia (sensor) g protein
59
Rac
Lamellipodia (leading edge) g protein
60
Filopodia fn
SENSOR 4 cell motility
61
LAMELLIPODIA FN
LEADING EDGE (CELL MOTILITY)
62
RAC FN
REARRANGES. Actin to STRETCH OUT FRONT IN LAMELLIPODIUM
63
Rho Rac Cdc42
Rho = STRESS FIBERS & FOCAL CONTACTS ``` Rac = lamellipodia (leading edge) CDC42 = filopodia (Sensor) ```
64
Order of jxns from top (apical) to bottom
Tight Adherens Desmosomes Gap Hemidesmosomes & focal adhesions
65
Adherens
Actin filament
66
Desmosones
IFs
67
Tight jxn adhesion proteins
CLAUDIN | OCCLUDIN
68
TIGHT jxn fn
Prevent membrane P's from slipping down / out of place Determine cell polarity (apical side) Allows diffusion of substances between cells (NOT FROM 1 cell to another)
69
Chron's and ulcerative colitis = issue with what?
TIGHT jxns (↓ occludin)
70
Adherens jxns
ACTIN - CATENIN - CADHERIN - CATENIN - ACTIN
71
Where will you find CATENIN and what does it do?
in ADHERENS JXNS Bind btw actin & cadherin
72
Cadherin dependent on ___
Ca++
73
Cadherin
Calcium
74
Demosomes parts
IF - DESMOPLAKEN - PLAKOGLOBIN - CADHERIN - PLAKOGLOBIN - DESMOPLAKEN - IF
75
DESMOSOME: anchor _____ Anchor P's = _______
Anchors IFs | Anchor P's = DESMOPLAKIN AND PLAKOGLOBIN
76
PEMPHIGUS
DESMOSOME CADHERIN DFCT
77
GAP JXN PARTS
6 CONNEXINS = 1 CONNEXON 2 CONNEXONS = 1 CHANNEL
78
GAP jxn fn
All cell to cell communication. Allow muscles to coordinate response and faster response. Mediate ELECTRICAL AND CHEMICAL COUPLING
79
GAP JXNS ALLOW FREE PASSAGE OF ---
IONS, SUGARS, AA, NUCLEOTIDES, 2ND MESSENGERS (cAMP...)
80
Electrical coupling fn of gap jxns
RAPID SPREAD OF APs
81
Chemical coupling fn of gap jxns
Allow 2nd messengers to flow from cell to cell
82
X -linnked charcot-marie tooth mutation
Connexin 32
83
Progressive degeneration of peripheral nerves Impaired deep tendon reflexes What is the mutation?
Connexin 32 Diz = charcot-marie-tooth neuropathy
84
Leukocyte rolling process
1) SELECTIN - R bind = WEAK so leukocyte ROLLS along endothelial cells 2) rolling ACTIVATES INTEGRINS ON LEUKOCYTES 3) integrins bind to ICAM = STRONG bind 4) start diapedesis
85
Child bruised Mut and disease
PLATELET INTEGRIN COMPLEX ABSENT (glycoprotein IIb-IIIa) Glanzmann's thrombasthenia
86
Glanzmann's thrombasthenia
Absense of PLATELET INTEGRIN
87
OSTEOGENESIS IMPERFECTA
MUT COLLAGEN I
88
EHLERS-DANLOS
MUT COLLAGEN 1, 3, 5
89
ALPORT
MUT COLLAGEN 4 RENAL FAILURE because THICKENING
90
GOODPASTURE SYNDROME
MUT COLLAGEN 4 RENAL FAIL
91
EPIDERMOLYSIS BULLOS
MUT COLLAGEN 7 HEMIDESMOSOME
92
OSTEOGENESIS IMPERFECTA MUT. And keyphrase
Mut collagen I Substitude of INVARIANT GLYCINE = severe phenottype BLUE SCLERA OI TYPE 2 = FATAL
93
WHICH TYPE. Of ehlers danlos = vascular dfcts and it is a mut in WHICH TYPE of collagen?
Type 4 = collagen 3 mut
94
Alport mutation
Mut ALPHA 5 CHAIN OF type 4 collagen Nephritis & DEAFNESS
95
Nephritis and deafness
Alport | A5 of t4 coll
96
Alport
Mutation
97
Goodpasture
Auto-immune
98
HSPG PERLECAN IS RICH IN WHICH REGION?
BASAL LAMINA
99
GAGs have what relation and function with relation to the KIDNEY?
GAGs serve as a SIZE-SELECTIVE and CHARGE SELECTIVE BARRIER
100
Hyperglycemia does what to HSPG?
↓ reg hspg → collagen glycosylation and cross linking. Glomerular basal mem THICKENS with ↑ in collagen and ↓ in HSPG Note: Lots of HSPG perlecan in BL of glomerulus. ↑ BG down reg's HSPG → causes collagen to glycosylate & cross-link → basal mem thickens = harder and needs ↑ P of blood to filter

MCB I (5 decks)

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