Epithelial Architecture And Renewal Flashcards

1
Q

Cell ____________ refers to attachment to adjacent cells

A

Coherence

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2
Q

Cell ____________ refers to attachment to ECM

A

Adherence

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3
Q

The intracellular domain provides anchorage for _______ filaments

These anchor proteins include ________, which are important signaling molecules that may play a role in cancer

A

Actin

Catenins (beta, p120, gamma-plakoglobin)

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4
Q

What are the 3 types of cytoskeletal filaments in order of smallest diameter –> largest diameter?

A

Microfilaments (actin)

Intermediate filaments (keratin)

Microtubules (tubulin)

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5
Q

Microtubules are composed of alpha- and beta-_________

A

Tubulin

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6
Q

Microtubules undergo polymerization and depolymerization at the ______ end

_______ is required for polymerization

A

Plus

GTP

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7
Q

How does the stability of microtubules compare to actin filaments?

A

Microtubules are more stable than actin filaments

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8
Q

What type of cytoskeletal filament is responsible for establishing cell polarity due to the MTOC?

A

Microtubules establish cell polarity due to the Microtubule Organizing Center

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9
Q

What are the 2 main functions of the MTOC?

A

Organization of eukaryotic flagella and cilia (motion)

Organization of mitotic and meiotic spindle apparatus (mitosis/meiosis)

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10
Q

Microtubules radiate from the MTOC with _____ ends extending out during cell division

A

Plus

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11
Q

What is another name for the MTOC?

A

Centrosome

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12
Q

What are intermediate filaments made of and what is their primary function?

A

Keratin

Imparts mechanical strength and anchors cell-cell and cell-matrix contacts

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13
Q

Cell-cell contacts are called ______________ and are anchored by what type of cytoskeletal filaments?

A

Desmosomes

Anchored by intermediate filaments

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14
Q

Cell-matrix contacts are called ______________ and are anchored by what type of cytoskeletal filaments?

A

Hemidesmosomes

Anchored by intermediate filaments

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15
Q

True or false: microtubules are the most stable of the cytoskeletal filaments

A

False, intermediate filaments are the most stable

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16
Q

How many different types of intermediate filaments are there?

A

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)
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17
Q

_____________ are also known as macula adhaerens

A

Desmosomes

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18
Q

Microfilaments are composed of two strands of ______, are flexible, and relatively strong

A

Actin

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19
Q

What are some of the functions of microfilaments?

A
Cytokinesis
Amoeboid movement
Cell motility
Changes in cell shape
Endocytosis/exocytosis
Cell contractility
Mechanical stability
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20
Q

_________ is a toxin from the death cap mushroom that binds to actin tightly and specifically to visualize it in cancer cells (e.g., melanoma)

A

Phalloidin

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21
Q

Plasma membrane protrusion and cell migration is driven by actin polymerization via what 3 types of projections?

A

Filopodia
Lamellipodia
Pseudopodia

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22
Q

_________ are also known as microspikes/spiky bundles, utilized in actin polymerization and are one-dimensional, found in fibroblasts

A

Filopodia

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23
Q

_________ are two dimensional/sheet-like structures formed by epithelial cells and fibroblasts (some neurons) for actin polymerization

A

Lamellipodia

[flat, protrusive veils]

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24
Q

_____________ are three-dimensional projections filled with actin-filaments, and are found in neutrophils

A

Pseudopodia

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25
Q

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
A

E. C and D

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26
Q

Actin filaments accumulate at the cell ___________

Nucleation occurs from the active ______ complex

A

Periphery

Arp

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27
Q

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

A

ARP

ActA; Arp 2/3

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28
Q

4 types of cell-cell junctions:

__________: holds cells together/in place

__________: separates apical and basolateral

__________: allows cell communication

__________: e.g. Neuromuscular junction

A

Anchoring

Occluding

Channel-forming

Signal-relaying

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29
Q

What are the 2 types of anchoring junctions?

A

Actin filament attachment sites (adherens junctions)

Intermediate filament attachment sites (desmosomes and hemidesmosomes)

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30
Q

What are the occluding junctions called in vertebrates?

A

Tight junctions

[septate junctions in invertebrates]

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31
Q

What are the channel-forming junctions called in animals?

A

Gap junctions

[plasmodesmata in plants]

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32
Q

What are the 3 major examples of signal-relaying junctions in the body?

A

Chemical synapses in the nervous system

Immunological synapses

Transmembrane ligand-receptor cell signal contacts (delta-notch, ephrin-eph, etc.)

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33
Q

What is the difference between homotypic/homophilic vs. heterophilic receptors?

A

Heterophilic have weak adhesion forces

Homotypic/homophilic have strong adhesion forces

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34
Q

_______ junctions seal the gap between epithelial cells

A

Tight

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35
Q

_______ junctions connect actin filament bundles in one cell with that in the next one

A

Adherens

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36
Q

___________ connect intermediate filaments in one cell to those in the next cell

A

Desmosomes

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37
Q

_______ junctions allow the passage of small water-soluble molecules from cell to cell

A

Gap

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38
Q

_____________ anchor intermediate filaments in a cell to the extracellular matrix

A

Hemidesmosomes

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39
Q

__________ ___________ adhesions anchor actin filaments in cell to the extracellular matrix

A

Actin-linked cell-matrix

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40
Q

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

A. Tight junctions

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41
Q

In order to fit through a gap junction, a molecule must be less than ______ Da

A

1000

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42
Q

Each gap junction is a single connexin, made up of six subunits called _________

A

Connexons

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43
Q

Gap junctions are not continuously open, they flip between open and closed states.

What is one condition that might cause gap junctions to close?

A

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

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44
Q

__________-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 ___________.

A

Integrin

Kinases

Collagen

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45
Q

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?

A

Macro-molecular assemblies (integrin-containing multi-protein complexes)

46
Q

What are 4 ligands for integrins?

A

Fibronectin
Vitronectin
Collagen
Laminin

47
Q

What types of molecules do integrins work alongside?

A

Cadherins
Ig superfamily
Selectins
Syndecans

48
Q

Cell-cell interactions consist of what 2 types of cell junctions? What is the transmembrane adhesion protein in cell-cell interactions?

A

Adherens junctions and desmosomes

Adhesion protein = cadherins

49
Q

What are the intracellular anchor proteins associated with adherens junctions?

A

Catenins

[also vinculin and alpha-actinin]

50
Q

What are the intracellular anchor proteins associated with desmosomes?

A

Plakoglobin (gamma-catenin), plakophilin, desmoplakin

51
Q

Cell-matrix interactions consist of what 2 types of cell junctions? What is the transmembrane adhesion protein associated with cell-matrix interactions?

A

Actin-linked cell-matrix adhesions and hemidesmosomes

Adhesion protein = integrins

52
Q

What are the intracellular anchor proteins associated with actin-linked cell-matrix adhesion junctions?

A

Talin, vinculin, alpha-actinin, filamin, paxillin, focal adhesion kinase (FAK)

[remember to associate FAK with actin and integrins!]

53
Q

What intracellular anchor proteins are associated with hemidesmosomes?

A

Plectin, dystonin

54
Q

What tends to happen in a mixture of cells where some express E-cadherin and some express N-cadherin?

A

They will sort into two separate groups of cells based on those expressing each type of cadherin

55
Q

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?

A

Those expressing high levels will clump together, and those with low levels will make up the perimeter

56
Q

What is a major biological example of the E-cadherin to N-cadherin switch?

A

Neural tube closure which occurs early in development

[this is mimicked in cancer metastasis]

57
Q

What type of cadherins are desmocollins and desmogleins?

A

Non-classical cadherins, associated with desmosomes

58
Q

What type of cadherins are calcium dependent?

A

Classical cadherins, associated with adherens junctions

59
Q

_______________ is the classical cadherin found in epithelial cells and the brain

A

E-cadherin

60
Q

_____________ is the classical cadherin found in muscle, nerve, lens cells, and fibroblasts.

A

N-cadherins

61
Q

___________ is the classical cadherin found in endothelial cells

A

VE-cadherin

62
Q

________________ is the classical cadherin found in the placenta and epidermis

A

P-cadherin

63
Q

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.

A

Solid; low; weak

Easily; signaling

64
Q

_____________ 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

A

Desmosomes

Desmocollin-2

[desmocollin is not properly inserted into the membrane]

65
Q

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

A

Desmoglein 1 (usually present in all layers of the epidermis)

66
Q

Which of the desmogleins is present in the basal and spinous layers?

A

Desmoglein 3

67
Q

The ECM is secreted largely by ______________

A

Fibroblasts

68
Q

True or false: the ECM is not plentiful in epithelial tissue

A

True; there is only a thin mat called the basal lamina

69
Q

The ECM is not plentiful in epithelial tissue, where is it plentiful?

A

Connective tissue

70
Q

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 ____________

A

Cytoskeletal filaments

Tension; compression

71
Q

What underlies all epithelial cells as well as surrounds individual cells, forming the mechanical/functional barrier?

A

The basal lamina

72
Q

The basal lamina functions as a ________ in kidney glomeruli

A

Filter

73
Q

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.

A

Connective tissue

Polarity

Proteins

74
Q

The basal lamina is synthesized by ______________ on one side, and the __________ on the other side.

A

Epithelial cells; stroma (CT)

75
Q

What are the 2 main classes of extracellular macromolecules?

A

Fibrous proteins (usually glycoproteins)

Glycosaminoglycan (GAGs - polysaccharide chain. Called a proteoglycan when covalently linked to a protein)

76
Q

During collagen biosynthesis, where does the hydroxylation of proline and lysine residues occur, as well as the glycosylation of selected hydroxylysine residues?

A

Lumen of the ER

77
Q

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)

A

Preprocollagen

Tropocollagen; disulfide

Secretory vesicles

78
Q

What type of collagen is also considered a proteoglycan?

A

FACIT (Fibril Associated Collagens with Interrupted Triple Helices)

This is a non-fibrillar collagen that attaches to the surfaces of fibrillar collagens

79
Q

What are the most common proteins (collagen types) in humans?

A

Types I, II, and III

80
Q

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

A

Polymers

Lysine

Bundles

81
Q

Connective tissue is constantly remodeled by what enzymes?

A

Prolyl and lysl hydroxylases

[this is deficient in disease states where the person cannot make collagen — because they cannot hydroxylate proline!]

82
Q

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?

A

Iron (Fe2+)

Ascorbate

83
Q

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?

A

Elastin and fibrillin

84
Q

________ _________ 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.

A

Ehlers-Danlos

85
Q

Which layer of the skin provides toughness and is rich in collagen?

A

Dermis

86
Q

Which layer of the skin is the fatty subcutaneous layer?

A

Hypodermis

87
Q

Which layer of the skin creates a water barrier and is made up of epithelial cells?

A

Epidermis

88
Q

Which layer of the skin contains keratinocytes, melanocytes, and Langerhans cells?

A

Epidermis

89
Q

Blood vessels are lined with polarized ___________ cells and serve to supply nutrients and O2, as well as remove waste products

A

Endothelial

90
Q

__________ and ___________ in the skin provide defense against microbes and pathogens

A

Macrophages

Dendritic cells

91
Q

_________ present in the skin provide adaptive immune responses

A

Lymphocytes

92
Q

What controls numbers of stem cells?

A

Contact with the basal lamina, once contact is lost, the cells will begin to differentiate

93
Q

Which aspect of neuron-like cells detects the change in membrane potential, the apical or basolateral side?

A

Apical. Basolateral creates the synapse to relay sensory info to the brain

94
Q

For olfactory receptors, one receptor type binds a single class of odorant (ligand). Ligands bind with ________ affinity

A

Variable

95
Q

What type of receptors are associated with olfaction?

A

GPCRs –> AC –> cAMP –> influx of Na and Ca

96
Q

The relay stations in the brain for olfactory signals are ___________, located in olfactory bulbs

A

Glomeruli

97
Q

Humans have 1000 genes that encode olfactory receptors, but they are mostly ___________

A

Pseudogenes

98
Q

How long do the olfactory neurons last before they are renewed?

A

1 month

99
Q

_________ 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

A

Neural
Basal
Axonal guidance

100
Q

Loss of olfaction may serve as a biomarker for what types of diseases?

A

Neurodegenerative diseases like Parkinson’s and Alzheimers

101
Q

_____________ refers to cell movement along the gradient of a diffusible signal

A

Chemotaxis

102
Q

_____________ GTPases trigger global structural rearrangements using a variety of external signals and cell-surface receptors. The signals converge inside the cell

A

Rho

103
Q

What monomeric GTPase proteins are members of the Rho family?

A

Cdc42
Rac
Rho

[these cycle between GTP bound active form and inactive GDP bound form]

104
Q

____________ cells refers to a time when actin is actively maintaining a resting state (not static). There are relatively minimal rearrangements

A

Quiescent

105
Q

Rho activation promotes the bundling of actin filaments which then leads to what?

A

Stress fiber formation

106
Q

_______ activation promotes actin polymerization at the cell periphery, as well as formation of lamellipodia extensions

A

Rac

107
Q

Cdc42 activation is associated with formation of ___________

A

Filopodia

[note: Rho –> stress fiber formation, Rac –> lamellipodia, Cdc42 –> filopodia]

108
Q

Ligand binding the front of a cell stimulates a GPCR, Rac activates _________ complex and forms ____________, and later triggers the activation of ______

A

ARP2/3 complex
Lamellipodia
Rho

109
Q

Rac and Rho activation pathways are mutually antagonistic. Rho dominates in the _______, while Rac dominates in the ________

A

Rear; front

[this enables cell polarity]

110
Q

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

A

Actin; 70