Epithelial Architecture And Renewal Flashcards
Cell ____________ refers to attachment to adjacent cells
Coherence
Cell ____________ refers to attachment to ECM
Adherence
The intracellular domain provides anchorage for _______ filaments
These anchor proteins include ________, which are important signaling molecules that may play a role in cancer
Actin
Catenins (beta, p120, gamma-plakoglobin)
What are the 3 types of cytoskeletal filaments in order of smallest diameter –> largest diameter?
Microfilaments (actin)
Intermediate filaments (keratin)
Microtubules (tubulin)
Microtubules are composed of alpha- and beta-_________
Tubulin
Microtubules undergo polymerization and depolymerization at the ______ end
_______ is required for polymerization
Plus
GTP
How does the stability of microtubules compare to actin filaments?
Microtubules are more stable than actin filaments
What type of cytoskeletal filament is responsible for establishing cell polarity due to the MTOC?
Microtubules establish cell polarity due to the Microtubule Organizing Center
What are the 2 main functions of the MTOC?
Organization of eukaryotic flagella and cilia (motion)
Organization of mitotic and meiotic spindle apparatus (mitosis/meiosis)
Microtubules radiate from the MTOC with _____ ends extending out during cell division
Plus
What is another name for the MTOC?
Centrosome
What are intermediate filaments made of and what is their primary function?
Keratin
Imparts mechanical strength and anchors cell-cell and cell-matrix contacts
Cell-cell contacts are called ______________ and are anchored by what type of cytoskeletal filaments?
Desmosomes
Anchored by intermediate filaments
Cell-matrix contacts are called ______________ and are anchored by what type of cytoskeletal filaments?
Hemidesmosomes
Anchored by intermediate filaments
True or false: microtubules are the most stable of the cytoskeletal filaments
False, intermediate filaments are the most stable
How many different types of intermediate filaments are there?
6 types
Type 1 = acidic Type 2 = basic Type 3 = forms homo- and heteropolymeric proteins Type 4 = neurofilaments Type 5 = nuclear envelope Type 6 = nestin (radial growth of axon)
_____________ are also known as macula adhaerens
Desmosomes
Microfilaments are composed of two strands of ______, are flexible, and relatively strong
Actin
What are some of the functions of microfilaments?
Cytokinesis Amoeboid movement Cell motility Changes in cell shape Endocytosis/exocytosis Cell contractility Mechanical stability
_________ is a toxin from the death cap mushroom that binds to actin tightly and specifically to visualize it in cancer cells (e.g., melanoma)
Phalloidin
Plasma membrane protrusion and cell migration is driven by actin polymerization via what 3 types of projections?
Filopodia
Lamellipodia
Pseudopodia
_________ are also known as microspikes/spiky bundles, utilized in actin polymerization and are one-dimensional, found in fibroblasts
Filopodia
_________ are two dimensional/sheet-like structures formed by epithelial cells and fibroblasts (some neurons) for actin polymerization
Lamellipodia
[flat, protrusive veils]
_____________ are three-dimensional projections filled with actin-filaments, and are found in neutrophils
Pseudopodia
Which of the following are small G-proteins (GTPase-dependent Rac and Rho)?
A. Actin filaments B. Lamellipodia C. Filopodia D. Microvili E. C and D
E. C and D
Actin filaments accumulate at the cell ___________
Nucleation occurs from the active ______ complex
Periphery
Arp
Listeria monocytogenes is a bacteria that is ubiquitous in the soil and in fresh produce. It invades intestinal cells by attaching to receptors on enterocytes and mimicking ______ proteins that nucleate actin monomers.
Listeria presents a surface protein called _____, which activates the ______ complex
Growing filaments are the driving force of symptoms
ARP
ActA; Arp 2/3
4 types of cell-cell junctions:
__________: holds cells together/in place
__________: separates apical and basolateral
__________: allows cell communication
__________: e.g. Neuromuscular junction
Anchoring
Occluding
Channel-forming
Signal-relaying
What are the 2 types of anchoring junctions?
Actin filament attachment sites (adherens junctions)
Intermediate filament attachment sites (desmosomes and hemidesmosomes)
What are the occluding junctions called in vertebrates?
Tight junctions
[septate junctions in invertebrates]
What are the channel-forming junctions called in animals?
Gap junctions
[plasmodesmata in plants]
What are the 3 major examples of signal-relaying junctions in the body?
Chemical synapses in the nervous system
Immunological synapses
Transmembrane ligand-receptor cell signal contacts (delta-notch, ephrin-eph, etc.)
What is the difference between homotypic/homophilic vs. heterophilic receptors?
Heterophilic have weak adhesion forces
Homotypic/homophilic have strong adhesion forces
_______ junctions seal the gap between epithelial cells
Tight
_______ junctions connect actin filament bundles in one cell with that in the next one
Adherens
___________ connect intermediate filaments in one cell to those in the next cell
Desmosomes
_______ junctions allow the passage of small water-soluble molecules from cell to cell
Gap
_____________ anchor intermediate filaments in a cell to the extracellular matrix
Hemidesmosomes
__________ ___________ adhesions anchor actin filaments in cell to the extracellular matrix
Actin-linked cell-matrix
Which of the following recruits the cytoskeleton, recruits signaling molecules, and forms a fence/wall, operating in vectorial transfer?
A. Tight junctions
B. Gap junctions
C. Desmosomes
D. Hemidesmosomes
A. Tight junctions
In order to fit through a gap junction, a molecule must be less than ______ Da
1000
Each gap junction is a single connexin, made up of six subunits called _________
Connexons
Gap junctions are not continuously open, they flip between open and closed states.
What is one condition that might cause gap junctions to close?
Cell stress/damage causes calcium ions to flow into the cell.
In order to prevent metabolites from leaking out and damaging neighboring cells, the damaged cell will close its gap junctions immediately
__________-mediated focal contacts exist as dimers in many combinations which dictate tissue homeostasis.
They are active via ___________ and actin nucleation.
They bind ECM proteins like laminin, fibronectin, elastin, and ___________.
Integrin
Kinases
Collagen
What type of focal adhesions transmit mechanical force via mechanical linkages to the ECM, and transmit regulatory signals between ECM-epithelial cells as a response to ECM adhesion and concentrate/direct numberous signaling proteins at sites of integrin binding?
Macro-molecular assemblies (integrin-containing multi-protein complexes)
What are 4 ligands for integrins?
Fibronectin
Vitronectin
Collagen
Laminin
What types of molecules do integrins work alongside?
Cadherins
Ig superfamily
Selectins
Syndecans
Cell-cell interactions consist of what 2 types of cell junctions? What is the transmembrane adhesion protein in cell-cell interactions?
Adherens junctions and desmosomes
Adhesion protein = cadherins
What are the intracellular anchor proteins associated with adherens junctions?
Catenins
[also vinculin and alpha-actinin]
What are the intracellular anchor proteins associated with desmosomes?
Plakoglobin (gamma-catenin), plakophilin, desmoplakin
Cell-matrix interactions consist of what 2 types of cell junctions? What is the transmembrane adhesion protein associated with cell-matrix interactions?
Actin-linked cell-matrix adhesions and hemidesmosomes
Adhesion protein = integrins
What are the intracellular anchor proteins associated with actin-linked cell-matrix adhesion junctions?
Talin, vinculin, alpha-actinin, filamin, paxillin, focal adhesion kinase (FAK)
[remember to associate FAK with actin and integrins!]
What intracellular anchor proteins are associated with hemidesmosomes?
Plectin, dystonin
What tends to happen in a mixture of cells where some express E-cadherin and some express N-cadherin?
They will sort into two separate groups of cells based on those expressing each type of cadherin
What tends to happen in a group of cells with some expressing high levels of E-cadherin and some expressing low levels of E-cadherin?
Those expressing high levels will clump together, and those with low levels will make up the perimeter
What is a major biological example of the E-cadherin to N-cadherin switch?
Neural tube closure which occurs early in development
[this is mimicked in cancer metastasis]
What type of cadherins are desmocollins and desmogleins?
Non-classical cadherins, associated with desmosomes
What type of cadherins are calcium dependent?
Classical cadherins, associated with adherens junctions
_______________ is the classical cadherin found in epithelial cells and the brain
E-cadherin
_____________ is the classical cadherin found in muscle, nerve, lens cells, and fibroblasts.
N-cadherins
___________ is the classical cadherin found in endothelial cells
VE-cadherin
________________ is the classical cadherin found in the placenta and epidermis
P-cadherin
Cadherins are the principle components of adherens junctions and desmosomes and cluster at sites of cell-cell contacts.
They are found in most _____ tissues and have _____ affinity, with strong attachments through many _____ bonds.
They are ______ disassembled and act as cell ___________ centers.
Solid; low; weak
Easily; signaling
_____________ are cell junctions that have been implicated in arrhythmogenic right ventricular cardiomyopathy (ARVC) due to missense mutations in _________________, which causes cardiac death at a young age
Desmosomes
Desmocollin-2
[desmocollin is not properly inserted into the membrane]
Pemphigous foliaceus is an autoantibody-mediated blistering disorder in which antibodies against ____________ cause a loss of adhesion of keratinocytes in the superficial layers of the epidermis
Desmoglein 1 (usually present in all layers of the epidermis)
Which of the desmogleins is present in the basal and spinous layers?
Desmoglein 3
The ECM is secreted largely by ______________
Fibroblasts
True or false: the ECM is not plentiful in epithelial tissue
True; there is only a thin mat called the basal lamina
The ECM is not plentiful in epithelial tissue, where is it plentiful?
Connective tissue
Mechanical stresses are transmitted from cell to cell by ___________ _____________ anchored to cell-matrix and cell-cell adhesion sites.
The extracellular matrix directly bears mechanical stresses of __________ and ____________
Cytoskeletal filaments
Tension; compression
What underlies all epithelial cells as well as surrounds individual cells, forming the mechanical/functional barrier?
The basal lamina
The basal lamina functions as a ________ in kidney glomeruli
Filter
The basement membrane separates cells from _________ _________.
It is a selective filter that helps determine cell _________.
It influences cell metabolism and organizes _________in adjacent cell membranes.
It promotes cell survival, proliferation, differentiation, and migration.
Connective tissue
Polarity
Proteins
The basal lamina is synthesized by ______________ on one side, and the __________ on the other side.
Epithelial cells; stroma (CT)
What are the 2 main classes of extracellular macromolecules?
Fibrous proteins (usually glycoproteins)
Glycosaminoglycan (GAGs - polysaccharide chain. Called a proteoglycan when covalently linked to a protein)
During collagen biosynthesis, where does the hydroxylation of proline and lysine residues occur, as well as the glycosylation of selected hydroxylysine residues?
Lumen of the ER
The synthesis of collagen begins with synthesis of __________ and insertion of procollagen molecule into the lumen of the ER
This is followed by hydroxylation of Pro and Lys and glycosylation of hydroxylysine residues in the ER lumen.
Then there is self-assembly of the __________ molecule, initiated by ________ bond formation in the carboxyterminal extensions; triple helix formation (in the ER lumen and golgi).
Procollagen is prepared for secretion from the cell in _________ ________.
Then there is cleavage of propeptides, removing the amino- and carboxy-terminal extensions, and self-assembly of the collagen molecules into fibrils and then fibers (extracellular)
Preprocollagen
Tropocollagen; disulfide
Secretory vesicles
What type of collagen is also considered a proteoglycan?
FACIT (Fibril Associated Collagens with Interrupted Triple Helices)
This is a non-fibrillar collagen that attaches to the surfaces of fibrillar collagens
What are the most common proteins (collagen types) in humans?
Types I, II, and III
Collagen fibrils are higher order ___________ that make up a thin structure.
The fibrils are strengthened by covalent cross-linking between _______ residues.
The fibrils aggregate into _______ that are several micrometers in diameter
Polymers
Lysine
Bundles
Connective tissue is constantly remodeled by what enzymes?
Prolyl and lysl hydroxylases
[this is deficient in disease states where the person cannot make collagen — because they cannot hydroxylate proline!]
Scurvy may result from the loss of a cofactor necessary in the conversion of 2-oxoglutarate to succinate using prolyl hydroxylase. What 2 cofactors may be deficient in scurvy?
Iron (Fe2+)
Ascorbate
Those with Marfan’s syndrome are at high risk of acute aortic rupture due to a weakened aorta. They are also at higher risk of aortic aneurism and mitral valve prolapse. What 2 elastic fibers tend to be deficient in those with Marfan’s?
Elastin and fibrillin
________ _________ syndrome may be caused by a mutation in one of more than 12 different genes coding for either enzymes or fibrous proteins. The mutations alter the structure, production, or processing of collagen or proteins that interact with collagen, thus weakening connective tissue in the skin, bones, blood vessels, and organs.
Ehlers-Danlos
Which layer of the skin provides toughness and is rich in collagen?
Dermis
Which layer of the skin is the fatty subcutaneous layer?
Hypodermis
Which layer of the skin creates a water barrier and is made up of epithelial cells?
Epidermis
Which layer of the skin contains keratinocytes, melanocytes, and Langerhans cells?
Epidermis
Blood vessels are lined with polarized ___________ cells and serve to supply nutrients and O2, as well as remove waste products
Endothelial
__________ and ___________ in the skin provide defense against microbes and pathogens
Macrophages
Dendritic cells
_________ present in the skin provide adaptive immune responses
Lymphocytes
What controls numbers of stem cells?
Contact with the basal lamina, once contact is lost, the cells will begin to differentiate
Which aspect of neuron-like cells detects the change in membrane potential, the apical or basolateral side?
Apical. Basolateral creates the synapse to relay sensory info to the brain
For olfactory receptors, one receptor type binds a single class of odorant (ligand). Ligands bind with ________ affinity
Variable
What type of receptors are associated with olfaction?
GPCRs –> AC –> cAMP –> influx of Na and Ca
The relay stations in the brain for olfactory signals are ___________, located in olfactory bulbs
Glomeruli
Humans have 1000 genes that encode olfactory receptors, but they are mostly ___________
Pseudogenes
How long do the olfactory neurons last before they are renewed?
1 month
_________ stem cells reside in olfactory epithelium and generate replacements for the lost neurons.
__________ stem cells have contact with the basement membrane; they divide and differentiate into olfactory neurons.
Odorant receptor proteins help establish ____________ __________ pathways, which allow the growth cone to migrate and establish connection with the correct glomerulus in the olfactory bulb
Neural
Basal
Axonal guidance
Loss of olfaction may serve as a biomarker for what types of diseases?
Neurodegenerative diseases like Parkinson’s and Alzheimers
_____________ refers to cell movement along the gradient of a diffusible signal
Chemotaxis
_____________ GTPases trigger global structural rearrangements using a variety of external signals and cell-surface receptors. The signals converge inside the cell
Rho
What monomeric GTPase proteins are members of the Rho family?
Cdc42
Rac
Rho
[these cycle between GTP bound active form and inactive GDP bound form]
____________ cells refers to a time when actin is actively maintaining a resting state (not static). There are relatively minimal rearrangements
Quiescent
Rho activation promotes the bundling of actin filaments which then leads to what?
Stress fiber formation
_______ activation promotes actin polymerization at the cell periphery, as well as formation of lamellipodia extensions
Rac
Cdc42 activation is associated with formation of ___________
Filopodia
[note: Rho –> stress fiber formation, Rac –> lamellipodia, Cdc42 –> filopodia]
Ligand binding the front of a cell stimulates a GPCR, Rac activates _________ complex and forms ____________, and later triggers the activation of ______
ARP2/3 complex
Lamellipodia
Rho
Rac and Rho activation pathways are mutually antagonistic. Rho dominates in the _______, while Rac dominates in the ________
Rear; front
[this enables cell polarity]
ARP2 and ARP3 closely resemble monomeric _________, and they serve as nucleation sites for new filaments. There is a distinctive ________ angle from the mother cell as branched networks are created
Actin; 70
