Final Flashcards
_______ is necessary to maintain tissue function
Cell Renewal
What cell types are capable of re-entering the cell cycle and replacing damaged/lost cells?
fibroblasts and endothelial cells
Describe why cell renewal is necessary to maintain tissue function
Most somatic cells are arrested in G0 and do not proliferate
Cells in tissues may be lost due to DNA damage, injury, apoptosis etc.
New cells must replace these damaged/dead cells in the tissue – cell renewal
What is endothelial cell proliferation is driven by?
The growth factor VEGF
What can damage to endothelial cells/blood vessels lead to?
Hypoxia – tissue is not receiving enough oxygen
What does tissue hypoxia promote?
vascular endothelial growth factor production (VEGF) secretion, which in turn promotes endothelial cell proliferation through RTK signaling
What do endothelial cell do in response to VEGF?
Endothelial cells proliferate and form new capillaries (angiogenesis), which innervates the hypoxic tissue with new blood vessels
Describe the four stages of Wound healing
- Hemostasis
- Inflammation
- Proliferation
- Remodeling
Describe the four stages of wound healing
Hemostasis – cessation of blood flow: blood vessels constrict to minimize blood flow/loss, platelets promote clot formation, fibrin (fibrous protein) cross links platelets in clot
Inflammation – immune cells travel from bloodstream to wound site, fluid build up and immune cell extravasation promoted by vasodilation of blood vessels (swelling), increasing blood flow (redness)
Proliferation – fibroblasts enter wound site and secrete ECM components including collagen, rebuilding lost ECM. Epithelial cells continue to proliferate and close wound, myofibroblasts help pull damaged tissue together, new blood vessels form to innervate newly formed tissue through angiogenesis
Remodeling – collagen fibers are remodeled (type III to type I), new epithelium is fully formed and scar tissue forms
What do fibroblasts differentiate into?
A specific subtype of fibroblast called the myofibroblast
When do myofibroblasts form?
Myofibroblasts form from differentiation of fibroblasts during wound healing
What do myofibroblasts do?
Myofibroblasts are contractile cells that promote wound healing by pulling damaged tissue together using smooth muscle type actin and myosin during the proliferation phase
This differentiation process is driven by mechanical tension and the cytokine transforming growth factor-β1 (TGF-β1)
What is the average lifespan of the human liver cells?
200-300 days
Describe two aspects of liver regeneration
- Liver cells are arrested in G0 but capable of re-entering cell cycle
- Liver regeneration is done by normal differentiated liver cells in response to specific extracellular signals
Describe a fact about rat liver removal
In rats, surgical removal of 2/3 of the liver leads to full regeneration of liver in a few days
What are most cells in adult tissues are replaced by?
The proliferation and differentiation of stem cells
Define stem cells
Stem cells - undifferentiated cells with the potential for self renewal and differentiation
What are stem cells capable of?
Stem cells are capable of asymmetric cell division, producing one stem cell and one differentiating cell through mitosis (can also produce two stem cells through mitosis)
What are trasit-amplifying cells?
undifferentiated cells in transition from stem to differentiated cell
Define differentiation
process of becoming a specialized cell type – involves large changes in gene expression (epigenetics, chromatin remodeling), also changes in cell morphology, metabolism etc.
What is a hematopoietic stem cell (HSC)?
a classic model of a self-renewing stem cell that gives rise to a multitude of differentiated cell types
Describe the different types of blood cells
Erythrocytes – red blood cells, transport oxygen and CO2
Platelets – fragments of megakaryocytes that promote clot formation
Macrophages – phagocytic cells involved in both innate and adaptive immunity
Granulocytes – white blood cells with immune functions, characterized by secretory granules
B and T lymphocytes (B cells and T cells)– white blood cells involved in adaptive immune response
How many blood cells does the human body produce in a day?
100 billion
What does the maintenance of blood cell populations depend on?
Adult blood cells do not proliferate – maintenance of cell populations depends on hematopoietic stem cell population maintenance
What do all of the different types of blood cells develop from?
hematopoietic stem cells in the bone marrow
What makes bone marrow transplants possible?
The vast potential of HSCs
What are some of the most proliferative stem cells in the body?
Intestinal crypt stem cells
What is the lifespan of the intestinal epithelium?
A few days, exposed to harsh environment, billions of cells shed each day
What replaces lost epithelial cells in the intestines?
Stem cells at the base of intestinal crypts continually divide and replace lost epithelial cells
What makes up 2/3 of the intestinal crypts?
Transit amplifying cells
What is a niche?
An extracellular environment that maintains stem cells
Stem cells reside within specific microenvironments called _______
niches
What do niches provide?
provides environmental signals that maintain stem cells/balance their self renewal and differentiation
In the intestinal crypt, what helps maintain intestinal crypt stem cells?
Paneth cells and Wnt-producing fibroblasts secrete Wnt polypeptides that help maintain intestinal crypt stem cells
Describe the several stem cell compartments of mammalian skin
Epidermal stem cells differentiate into transit-amplifying cells, which differentiate into new epidermis cells
Bulge stem cells give rise to transit-amplifiying matrix cells, which differentiate and form the hair shaft
Sebaceous gland stem cells maintain the sebaceous gland, which secretes oils to protect the skin
What is the muscle stem cell?
The satellite cell
Describe stem cells in the skeletal muscle
Satellite cells – stem cells in muscles located beneath basal lamina of muscle fibers
The progeny cells of satellite cells differentiate and fuse into new muscle fibers
True or False: Skeletal muscle is capable of rapid regeneration in response to damage (injury, exercise)
True
Embrionic stem cells are _______
totipotent: able to give rise to all tissues
Give the hierarchy of stem cell differentiation ability
Totipotent > Pluripotent > Multipotent
what kind of state are embryonic stem cells grown in?
An undifferentiated state.
Embryonic stem cells can be induced to form ______ and then differentiate into a variety of cell types.
embryoid bodies
Describe Somatic cell nuclear transfer and cloning
- Nuclei from adult somatic cells are transferred to enucleated oocyte
- 1-2% of embryos generated give rise to adult with identical genetics (clone)
- Epigenetic reprogramming necessary to give
rise to all cells in clone
- Limited lifespan
Describe Therapeutic cloning
- Similar process (adult somatic cell nuclear transfer)
could be utilized for therapeutic cloning - Generation of clonal embryonic stem cells
- Stem cells could then be differentiated in vitro to
give rise to cells and tissues for transplant
- Identical genetics – no risk of
transplantation rejection
What TF are able to reprogram somatic cells to a pluripotent state?
A cocktail of transcription factors termed the Yamanaka factors
Describe how we are able to reprogram somatic cells to a pluripotent state
- A cocktail of transcription factors, termed the Yamanaka factors, are able to reprogram somatic cells to a pluripotent state.
- This allows adult fibroblast cells to be “reprogrammed” into induced pluripotent stem cells through the expression of specific transcription factors.
- Takashi and Yamanaka introduced Oct4, Sox2, Klf4, and c-Myc transcription factors through a retroviral vector which infects the somatic cell.
- An induced pluripotent stem cell is then produced, which functions similar to embryonic stem cells – capable of differentiating into all cell types.
How do Yamanaka factors work?
They act synergistically to repress differentiation genes and open chromatin and activate transcription of pluripotency genes.
- Yamanaka factors form a positive feedback autoregulatory loop that maintains pluripotency in both induced and embryonic stem cells
- The function of these transcription factors activates transcription of pluripotency-promoting genes and represses expression of differentiation genes
What is c-Myc?
A proto-oncogene that promotes proliferation of stem cells – can lead to risk of tumor development following stem cell implantation
What was found to be dispensable in the production of induced pluripotent stem cells?
Nanog
What is Transdifferentiation?
The direct conversion of cells from one fate to another.
The direct differentiation of a differentiated adult cell into another differentiated lineage
True or false: Differentiated blood cells can also transdifferentiate to other blood cell types, but NOT hematopoietic stem cells
False: they CAN transdifferentiate into HSCs
(ex: leukocyte can go to granulocyte; leukocyte CAN ALSO go to hematopoietic stem cell)
How can transdifferentiation occur?
Through mutations accumulated in cancer cells i.e. leukemia, lymphomas.
What is the extracellular matrix (ECM)
A network of proteins, polysaccharides, and other components that fills the spaces between cells and binds cells and tissues together
Where is ECM most abundant?
In connective tissues – tendons, bones, cartilage
What is the basal lamina?
A thin sheet of ECM that supports epithelial cells, also surrounds muscles and peripheral nerves
What is ground substance?
Fibrous proteins embedded in a gel-like matrix of polysaccharides that makes up the ECM
What are fibroblasts?
Specialized cells that secrete ECM
What are chondrocytes?
Chondrocytes secrete collagen and other extracellular matrix components to form and maintain cartilage
What is the most abundant ECM protein?
collagen
What kind of structure does collagen form?
Individual collagen polypeptides wind together forming a triple helical structure resembling a rope
What does the triple helix domain of collagen contain?
It contains regular G(glycine)-X(often proline)-Y(often hydroxyproline) repeats to allow for tight packing (glycine required in every 3rd position)
What is Hydroxyproline
A modified proline residue formed in the ER lumen
True or false: Collagen helices are stratified and cross linked into fibrils
True
What do Fibrils help contain?
The gaps between collagen triple helices that contribute to flexibility
Do fibrils form inside the cell?
No, Fibrils do not form within cells – procollagen is cleaved to collagen following secretion from the cell
What has has regular breaks in its helical domain?
Type IV Collagen
Describe Type IV collagen
Type IV collagen forms networks rather than fibers – key role in formation of basal lamina
G-X-Y domain in helical region is interrupted by nonhelical domains – cannot form fibers
Type IV collagen is more flexible than fiber-forming collagens
What is the makeup of a Glycosaminoglycan (GAGs) ?
repeated disaccharide chains which often contain sulfate groups
Where are GAGs formed?
The golgi
What do GAGs do?
GAGs help form a hydrated gel-like network in the extracellular matrix
GAGs often possess sulfate modifications which confer a negative charge – interact with positively ions and water molecules
What is the significance of Hyaluronan?
It is is the only GAG that forms long chains, all others are linked to proteins to form proteoglycans
What are Proteoglycans?
core proteins with numerous GAG chains
Proteoglycans contain many (over 100) GAG chains, each consisting of up to 100 sugar residues
Different GAG modification confer variable properties to different proteoglycans – highly diverse
What is Fibronectin?
- A functional scaffold connecting multiple ECM elements.
- An adhesion protein secreted primarily by fibroblasts
- Contains multiple binding sites that link ECM components to one another and to cells
- A dimer composed of two long (~2500AA) chains crosslinked by disulfide bonds
What do adhesion proteins do?
link components of the ECM to one another
What are lamins?
- Adhesion proteins that are the principal component of the basal lamina
- T-shaped heterotrimeric proteins that can link together with one another to form extensive networks
What can Laminins interact with?
cell surface proteins (integrins), proteoglycans, and other adhesion proteins like nidogens
What are integrins?
Integrins are cell surface receptors that bind to ECM proteins, linking cells to the ECM
- heterodimeric proteins containing an alpha and beta subunit
- The alpha subunit binds to divalent cations (Mg2+, Ca2+) – regulates ligand/matrix binding
- 18 different alpha subunits + 8 different beta subunits – 24 different integrin complexes in humans
How are integrins are connected to the cytoskeleton?
via focal adhesions or hemidesmosomes
- Focal adhesions link intermediate filaments to the extracellular matrix – stable connections
- Focal adhesions link actin microfilaments to the extracellular matrix – less stable than hemidesmosomes
What are cell adhesion molecules are capable of?
highly selective homophilic (like with like) and heterophilic interactions
Certain adhesion molecule interactions form stable structures (adherens junctions, hemidesmosomes), others are transient
What is the immune response to pathogens is mediated by?
By the extravasation of leukocytes (white blood cells) from the bloodstream to sites of inflammation/infection
What do Selectins do?
mediate transient interactions between leukocytes and endothelial cells that line blood vessels
What do L-selectins on leukocytes bind to?
carbohydrates on the endothelial cell surface.
This represents a weak initial adhesion event that facilitates stronger integrin-ICAM (intercellular adhesion molecules) adhesions
What does the firm adhesion between leukocytes and endothelial cells allow for?
leukocytes to squeeze between endothelial cells and migrate into tissues
What are adherens junctions and desmosomes?
stable adhesions mediated by cadherins
What do adherins junctions do?
junctions link the actin cytoskeleton (microfilaments) of adjacent cells together and form adhesion belts
What do desmosomes do?
link intermediate filaments of adjacent cells together
Where do tight junctions form?
between strands of transmembrane proteins and separate the apical and basolateral domains
What do tight junctions prevent?
fluid and ion flow between cells – strong seals but weak adhesive strength, often associated with other junctions
What makes the most apical junctions on epithelial cells?
Tight junctions
What do gap junctions form?
a porous connection between cells
Gap junctions form direct connections between adjacent cells – share cytoplasmic components less than 1000 daltons in size (cAMP, Ca2+)
Describe the structure of a gap junction
Gap junctions are dodecameric (12 subunits) channels formed through the interactions of hexameric (6 subunits) connexons on adjacent cells
describe the structure of a connexon
Six connexins joined together
True or False: Gap junctions are dynamically regulated and can exist in open and closed conformations
True
True or false: A number of congenital diseases are due to defects in gap junctions
True
What are Plasmodesmata? Describe some of their characteristics
junctions in plant cells that have analogous functions to gap junctions
Due to cell walls, plant cells do not require cytoskeletal adhesions form stable associations with one another
Projection of smooth ER often found in plasmodesmata pore
Dynamically regulated similar to gap junctions (open/close)
What type of organisms are commonly used in research?
GMOs
- fruit fly
- c. elegans
- fish
- mouse
Describe some advantages and disadvantages to using drosophila as GMOs
Advantages:
Large community of researchers
gold standard in genetic tools
short generation time
Disadvantages:
Limited behavioral repertoire
Fewer shared genes with humans compared to rodents
What was the 2nd multicellular organism to have their genome sequenced?
drosphila
Describe some advantages and disadvantages to using mice as GMOs
Advantages:
- Really only mammalian model with well developed
genetic tools.
- Wide behavioral repertoire.
- Share many genes and pathways with humans:
applicability to human disease
Disadvantages:
- Significantly more difficult (and costly) to house than
most the other transgenic models.
Define a genetically modified mouse
- A mouse that has had its genome altered through the use of genetic engineering techniques.
What is the most commonly used organism for GMOs
Mice
- used for research or as animal models of human diseases
- also used for research on genes and genetic pathways.
How can we study the function of genes expressed throughout various tissues in an organism?
- Removing genes (knockouts)
- Expressing transgenes
- Marking cells that express a gene or are active
- Reducing gene expression (RNA interference)
- Activating or inhibiting cellular populations
experimentally
What is a knockout?
removal/inactivation of specific gene
How can knockouts can provide information about a gene’s function?
Comparing knockout and wild-type phenotypes can provide information on the knockout gene’s function
Give an example of a knockout
Leptin knockout
- fat mouse
- Removing leptin stops the mouse from feeling satiated
Describe the steps to making Genetically Engineered Mice through Homologous Recombination
- Make a DNA construct where gene of interest is
interrupted by a “marker” or selector gene
neo – Neomycin resistance gene is often used - Electroporate DNA construct into cultured
embryonic stem cells (ES) - Allow Homologous recombinationto take place
- Homology arms – long segments of genomic DNA
flanking the sequence to be inserted that
facilitate recombination - Homologous recombination - LOW FREQUENCY
EVENT
- Homology arms – long segments of genomic DNA
- Select cells that incorporated marker
- Inject stem cells into mouse blastocyst and implant
into foster mother mouse - Mice homozygous for mutated gene (knockout) can
be obtained through mating
Describe how “Knock in” mice can be generated
Can be generated through the same techniques
- Gene to be “knocked in” flanked by homology arms
- Homologous recombination will lead to the
incorporation of gene to be “knocked in” at the
location of homology arm sequences in genome
What are humanized mice
Mice where certain genes have been replaced with homologous human gene
What does CRISPR allow for?
- Specifically targeted alterations as small or as large
as needed - Circumvents the “randomness” of mutations and
homologous recombination - Makes anything a “model system” because only a
small part of the genome needs to be known
What is Cas9?
Cas9 – “CRISPR associated protein”, nuclease that acts as the “scissors”
What does Single guide RNA (sgRNA) do?
It targets specific gene sequence in genome
- Nucleotides in guide RNA are complementary to
nucleotides in DNA sequence
Describe DNA editing using CRISPR-Cas9
- Two DNA sequences introduced to cell
- One codes for Cas9 protein
- Other codes for sgRNA - Cas9 can only digest DNA near protospacer adjacent
motif (PAM) sites (NGG) - sgRNA contains 20bp sequence specific for sequence
in genome immediately 5’ to endogenous PAM site
Describe how CRISPR-Cas9 can be used to knock out and knock in genes
Double stranded breaks can be repaired through
two mechanisms
- Non-homologous end joining (NHEJ) – broken DNA
ends are rejoined, often includes insertion or
deletion
- Frameshift resulting from indel often leads to
premature stop codon - Homology-directed repair (HDR) – DNA construct
with homology arms is used as a template for
homologous recombination
Describe how you can generate knockouts/knock-ins in Mice through CRISPR
- A guide RNA (sgRNA) is designed to target a specific
sequence in the gene of interest.
-The sgRNA is complementary to the DNA
sequence near the gene’s coding region. - The CRISPR-Cas9 system, which consists of the Cas9
protein (which cuts DNA) and the sgRNA (which
guides Cas9 to the target site), is introduced into
either the mouse embryonic stem cells (ESCs) or
fertilized eggs. - The Cas9 protein then creates a double-stranded
break at the target site in the genome. - This break triggers the cell’s DNA repair mechanisms,
typically via non-homologous end joining (NHEJ). - After CRISPR editing, the cells or embryos are
screened for successful gene disruption. - If embryos are used, they are implanted into a
surrogate mother, and the mice that carry the
knockout allele in their genome are bred to establish
a knockout lineage.
How was RNAi-mediated mRNA degradation first discovered?
- Phenomenon first described after injecting single-
stranded RNAs into petunias to alter flower color
-Inexplicably led to loss of color… - Similar observation described by Craig Mello and
Andrew Fire in C. elegans. - They showed that a dsRNA (with sequence region of
mRNA) potently induced the degradation of that
mRNA. - Antiviral response; new paradigm for gene
regulation
How does RNA interference with siRNA reduce expression of a target gene?
- RNAi allows researchers to lower or “knock down”
target gene expression without removing the gene
from the genome. (KNOCK DOWN not REMOVE) - dsRNA (natural or artificial) is cleaved by the
endonuclease Dicer. - The RISC complex is then recruited to siRNA duplex,
which unwinds to form ssRNA. - The RISC complex then scans to find mRNA which is
complementary to associated ssRNA. - Once found, a component of RISC cleaves the mRNA,
leading to its degradation and ultimately a reduced
expression of whatever gene it encoded.
Describe the makeup of microtubules?
polar, hollow filaments made of two subunits
Microtubules are formed through dimeric associations of alpha and beta tubulin
These dimers assemble into ring-shaped, hollow filaments approximately 25nm in diameter (actin microfilaments – 7nm)
Alpha and beta tubulin are _______
obligate heterodimers
Describe the obligate heterodimer of alpha and beta tubulin?
Tubulin dimers form shortly after protein synthesis – obligate heterodimers
Alpha and beta tubulin bind to GTP/GDP which influence their association dynamics.
Beta tubulin has GTPase activity;alpha tubulin does not
MTs have a fast growing ___ end and a disassembling ____end
plus, minus
What is added the plus end of microtubules?
GTP bound tubulin dimers are added to the + end of microtubules
What disassociates from the minus end of microtubules?
GDP bound tubulin dimers dissociate from the - end of microtubules
How can a a GTP cap form?
If GTP-tubulin dimers are rapidly added to the + end
What does a GTP cap influence?
The presence of a GTP cap at the plus end will influence growth/shrinkage kinetics – prevents catastrophe
Where are minus ends usually anchored?
at the centrosome or microtubule organizing center (MTOC)
Describe the factors that influence dynamic instability
Microtubule plus ends will grow as long as new GTP bound tubulin dimers are added faster than GTP is hydrolyzed within the tubule
Minus ends are usually anchored at the centrosome or microtubule organizing center (MTOC) to prevent depolymerization
Microtubule shrinkage will occur at the plus end if GTP hydrolysis occurs more rapidly than GTP bound tubulin dimers are added to the tubule
How are Microtubule growth and shrinkage dynamically regulated?
Microtubule-associated proteins (MAPs)
Microtubule polymerases bind to the + end and increase the incorporation of GTP bound tubulin heterodimers by ~10 fold
Give an example of a catastrophe factor
Microtubule depolymerases are a class of MAPs that bind to the plus end and accelerate the dissociation of GTP-bound tubulin dimers from the + end, leading to the loss of the GTP cap and promoting catastrophe
Give an example of a rescue factor
Other MAPs (CLASPs), bind to microtubules undergoing catastrophe and prevent further depolymerization, also promote rescue (sudden switch back to growth)
What are the two primary microtubule organizing centers (MTOC) in the cell
the centrosome and basal body
Centrosomes are the primary MTOC in animal cells – basal bodies are nucleation sites for MT associated with cilia and flagella
What do Microtubule organizing centers do?
They nucleate new microtubules and serve as an anchoring site for microtubule minus ends – preventing minus end disassembly
When are centrosomes duplicated?
during the G1/S transition in mitosis
What is the core of the centrosome?
The centriole
What does each centrosome contain?
two centrioles organized perpendicularly from one another
Describe the structure of a centriole
cylindrical structures composed of 9 microtubule triplets arranged in a circle/ring
True or false: Centrioles are not found in basal bodies
False. They are found in basal bodies
What is gamma tubulin and where is it found?
– tubulin species that nucleates microtubule assembly – forms gamma tubulin ring complex from which microtubule filaments “grow”
- found in the centrosome
What surrounds each centriole, what does it contain, and how does it function?
Pericentriolar material surrounds each centriole – contains gamma tubulin and functions as nucleation site for microtubule assemble
What are the two families of motor proteins are associated with microtubule filaments
kinesins and dyneins
Both families of motor proteins couple ATP hydrolysis to conformational changes in the motor protein, generating motion and force
What end of transport are each of the two families of motor proteins are associated with
Kinesins are responsible for plus end directed transport along the microtubules
Dyneins are responsible for minus end directed transport
What are the two types of dyneins and what do they control?
- Axonemal dyneins drive the motion of cilia
- cytoplasmic dyneins control vesicle/cargo transport
What are neuronal extensions are powered by
microtubule transport
How are Microtubules in axons organized
with minus ends facing cell body, plus ends facing axon terminus
How are Microtubules in dendrites organized?
bidirectionally
How are microtubules in dendrites and axons stabilized?
MAPs. MAP2 stabilizes dendritic microtubules, tau stabilizes axonal microtubules
What can form aggregates and tangles associated with neurodegenerative diseases?
Tau
What relies on microtubules for structural support and trafficking?
Dendrites and axons on neurons
How do Dynein and kinesin motors work to move organelles and vesicles?
In parallel.
Kinesins and dyneins combine to allow for bidirectional transport along microtubule filaments
Kinesins drive plus end directed transport
Dyneins drive minus end directed transport
Chromosome separation during mitosis requires ________
microtubules and motor proteins
Movement of spindle poles is mediated by molecular motors – kinesins (+) and dyneins (-)
Microtubules are highly associated with the ____
endoplasmic reticulum – vesicles originating in the ER for secretory pathway travel along microtubules
What helps extend ER to periphery of cell
microtubules
True or false: Microtubule associated motors are also responsible for positioning the ER (and other organelles) within the cell
True
What are two Specialized MT structures?
Cilia and flagella
Describe the two types of cilia
Primary cilia – sensory projections – contain receptors to detect extracellular signals
Motile cilia – cell movement
Both primary and motile cilia contain nine doublets of microtubules
Describe flagella
Flagella – long, threadlike extensions responsible for movement through whip-like motion
Where are cilia and flagella found
The plasma membrane
What do primary cilia lack?
dyenins
What do Motile cilia contain?
An extra central pair of microtubules as well as nexin proteins linking outer doublets together. Dynein motors are responsible for movement of outer doublets.
What is the radial spoke
A protein complex connecting the central pair and outer doublets of microtubules
What are both primary and motile cilia anchored to?
Basal bodies, which contain triplet microtubules and function as a MTOC
What is cilia movement coordinated by?
Dynein movement
The movement of dyneins linking outer doublets of microtubules together causes bending of microtubules and cilia movement
What are Intermediate filaments?
A diverse set of filament forming proteins
True or false: Intermediate filaments oligomerize from dimers and create polar filaments
False.
Yes, they oligamerize from dimers, but no, they do not create polar filaments.
How do intermediate filaments assemble?
High amount of diversity among intermediate filament proteins (size, AA sequence), but mechanism of assembly is similar
Monomers assemble into dimers through coiled-coil interactions
Dimers form tetramers through antiparallel interactions. These tetramers can join to form higher order oligomers
As both ends of intermediate filaments are the same, there is no polarity associated with intermediate filaments – no plus or minus ends
Intermediate filaments also do not have preferential assembly at each end – subunits can be exchanged along the length of the filament
What are the primary intermediate filament found in epithelial cells
keratins.
Keratin is also the primary component of hair, skin, and fingernails
What are desmosomes?
junctions between cells that adhere cells to one another
What are plakins?
The site of intermediate filament (keratin) attachment on a desmosome. They typically form a dense plaque on the face of the desmosome.
What do cadherin proteins do?
Cadherin proteins (desmoglein and desmocollin) link adjacent cells to one another
What do hemidesmosomes do?
Hemidesmosomes anchor the cell to the extracellular matrix, linking cell surface integrin proteins to intermediate filaments through plectin
What forms connections to other cytoskeletal systems?
Intermediate filaments
What also forms links between intermediate filaments to actin microfilaments and microtubules
plectin
What has important functions in tissue integrity?
Intermediate filaments like keratin
