Module 5: ECM Flashcards
The extracellular matrix contains many fibrous proteins and proteoglycans which have numerous functions such as:
- provide shape and structure
- provide lubrication
- provides an anchor point to allow cell adhesion
- allows communication between adjacent cells
Proteoglycans are highly charged protein/saccharide polymers ( > 95% carbohydrates) which prevent compression of ECM. Proteoglycans are composed of:
- Hyaluronic acid
- Chondroitin sulfate
- Dermatan sulfate
- Heparan sulfate
- Keratan sulfate
“KNOW”
_______ are the major protein components of the ECM.
Collagen
What are the structural characteristics of collagen?
Collagen fibers are flexible with high tensile strength
***Made up tropocollagen which is a triple helix made of 3 intertwined polypeptide chains in a repeating Motif (pattern)
Collagen forms a very specific structure: talk about this
- Each collagen protein has a unique left-handed helix
- There are three amino acids per turn of the protein
- Each turn of the helix has a specific sequence with the sequence Gly-Proline-Hydroxyproline
- Three helical collagen proteins come together to make a triple-stranded right-handed superhelical quaternary structure
What is the most common fibrillar collagen type in the body?
A. Type I B. Type II C. Type III D. Type IV E. Two of the above
A. Type I
What is the main function of fibrillar collagens?
tensile strength to skin, tendons and ligaments
Dermal collagen fibrils contain ______.
A. Type I B. Type II C. Type III D. Type IV E. Two of the above
E. Two of the above (type 1 and 3)
The basement membrane is made up of which type of nonfibrillar collagen?
A. Type I B. Type II C. Type III D. Type IV E. Two of the above
D. Type IV
____________ are thin layers of ECM that surround organs and generally provide a barrier between one tissue type and another.
Basement membranes
The main function of the basement membrane is _______.
to prevent migration of certain cell types between different tissues
What are the 7 steps in collagen synthesis?
- Preprocollagen is synthesized containing a signal sequence directing it to the lumen of the ER
- Removal of this signal sequence results in the formation of procollagen
- Post-translational modification occurs in the ER
- hydroxylases convert proline to hydroxyproline
- Glycosylation attaches sugars to the protein
- Disulfide linkages are incorporated - The disulfide linkages trigger formation of the triple helical structure producing tropocollagen
- Tropocollagen triple helices are transported to the Golgi and then exocytosed
- Tropocollagen is then converted to mature collagen by proteolysis
- Mature collagen can then be crosslinked to form the insoluble collagen fibers
- Preprocollagen
- Procollagen
- Post-translation modification
- Tropocollagen is formed
- Tropocollagen sent to Golgi
- Tropocollagen –> collagen
- Insoluble collagen
What are the collagen diseases?
- Scurvy (vitamin C)
2. Osteogenesis imperfecta (type 1 collagen)
_______ is produced fibroblasts and smooth muscle.
Elastin
Describe what Elastin is:
Elastin is a protein which forms elastic fibers in blood vessels, lungs, ligaments and skin
Elastin is formed as a single protein and has very little post-translational modification
Elastic fibers: allows response to stretch and distension
Elastin is produced by fibroblasts and smooth muscle cells
________ is an ECM protein that acts as an attachment point for other cellular and ECM components.
Fibronectin
note: fibronectin is involved in cell adhesion, cell migration, embryonic morphogenesis and cytoskeletal and ECM organization
______ is involved in cell adhesion, cell migration, embryonic morphogenesis and cytoskeletal and ECM organization.
Fibronectin
________ are the gel-forming portion of the ECM that is sometimes called the “ground substance” of the body.
Proteoglycans
Proteoglycans contain protein chains with large amount of complex carbohydrate (95%).
GAG: the carbohydrate portion of proteoglycans
- these carbohydrates are polyanionic due to uronic acid and high level of sulfation on the amino sugars (very good at sucking up water)
Proteoglycans _______.
A. >95% carbohydrate B. Linked w/ protein C. Usually unbranched D. Usually a specific repeating dimer of carbohydrates E. All of the above
E. All of the above
What are the 5 major proteoglycans of the ECM?
- Hyaluronic acid
- Chondroitin sulfate
- Dermatan sulfate
- Heparan sulfate
- Keratan sulfate
“Know what are the 5 types of major proteoglycans”
Which of the following major proteoglycans does NOT contain sulfation?
A. Hyaluronic acid B. Chondroitin sulfate C. Dermatan sulfate D. Heparan sulfate E. Keratan sulfate
A. Hyaluronic acid
Proteoglycans are primarily constructed in the ________.
Golgi
What are the functions of proteoglycans?
Their main role is to provide structural support to tissues, especially cartilage and connective tissue.
- they are commonly responsible for preventing compression stress in tissues due to their large negative charges
Proteoglycans have a large negative charge that leads to influx of water into the ECM
Many different proteoglycans can interact to produce large macromolecular bottlebrush-like structures called ________.
Aggrecans
- collagen and other ECM proteins are embedded in this matrix
Function of Proteoglycans
This highly charged matrix leads to several important properties of the ECM such as _________.
- rigidity
- flexibility
- compressibility
This overall structure allows tissues to withstand torsion and shock
What are the 3 MOST important characteristics of Hyaluronic Acid?
most likely an assessment question
- NO protein core
- No sulfation
- longest polysaccharide chain of all the GAGs
Which of the following is the most common GAG?
A. Hyaluronic acid B. Chondroitin sulfate C. Dermatan sulfate D. Heparan sulfate E. Keratan sulfate
B. Chondroitin sulfate
Which of the following GAGs is the major component of cartilage?
A. Hyaluronic acid B. Chondroitin sulfate C. Dermatan sulfate D. Heparan sulfate E. Keratan sulfate
B. Chondroitin sulfate
Which of the following is the most highly charged of all proteoglycans?
A. Hyaluronic acid B. Chondroitin sulfate C. Dermatan sulfate D. Heparan sulfate E. Keratan sulfate
D. Heparan sulfate
Heparan sulfate = anticoagulant properties
Which of the following is the most heterogenous GAG?
A. Hyaluronic acid B. Chondroitin sulfate C. Dermatan sulfate D. Heparan sulfate E. Keratan sulfate
E. Keratan sulfate
What is the difference in function between collagen and proteoglycans?
Collagen act as rebar providing strength and support
Proteoglycans act as an amorphous cement to tie everything together and provide rigidity
Describe the function and activation pathways of matrix metalloproteases (MMPs):
MMPs are responsible for digesting the structural components of ECM.
- MMPs are synthesized as zymogens and then activated in response to signaling events
- MMPs are very specific proteolytic proteins which can degrade other ECM proteins such as collagen, elastin, fibronectin and the protein core of proteoglycans as well as other MMPs
***Unlike other proteases, this family is dependent on a metal cofactor for activity (zinc)
ACTIVATION:
- to activate a zymogen MMP, the propeptide domain must be removed (cysteine switch).
(kinda like a pulling a barrier out to let electricity flow through)
- when the MMP contains the propeptide domain, the cysteine switch binds to the zinc atom and prevents its use by the enzyme
- when the propeptide domain is removed, the zinc is then available to conduct proteolytic activity
What are the 3 domains of MMPs?
- Propeptide domain (cysteine switch)
- Catalytic domain (binds zinc and allows proteolytic activity
- Haemopexin-like C-terminal domain
- binds to protein target (specificity)
- may bind to TIMPs (to inhibit activity)
- occasionally absent from some MMPs
Describe the catalysis of MMPs:
The MMP catalytic domain utilizes the zinc atom to activate a water molecule
This is where ZINC attaches
What are the 2 specific types of proteins that are important in ECM signaling?
- Integrin
2. Cytokines and growth factors
_______ are cell surface receptors linking the ECM to the cytoskeleton.
Integrin
- deformation of ECM can lead to activation of the integrin receptor
- the integrin can transmit the deformation to the cytoskeleton which can affect cellular structure
- additionally the integrin can directly activate cellular transcription factors leading to modification of gene expression (this can affect cell shape motility or the cell cycle
***Integrins are dimeric structures consisting of an alpha and beta subunit
***Integrin is a transmembrane signaler for ECM remodeling
Besides integrins, what is the other signaling molecule used in ECM remodeling?
- Cytokines
* ** common cytokine classes are interleukins and interferons
- each of these can signal cells to secrete MMPs and ready themselves for ECM remodeling
What are the 2 common cytokine classes that work in concert to signal cells to secrete MMPs and ready themselves for ECM remodeling?
Interleukins and Interferons
“MAY BE TEST Q”
