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ACVD Exam > Keratinization > Flashcards

Keratinization Flashcards

1
Q

Describe keratinization

A

Process of cytodiferentiation that the keratinocyte undergoes when proceeding from their post germinative state (stratum basale) to the finally differentiated, hardened cells of the stratum corneum

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2
Q

Describe the mammalian cytoskeleton

A
  • Primary regulator of cell shape due to its intrinsic mechanical properties allowing it to resist deformation as well as provide contractility
  • Generates forces on the surface of the cell to influence cell morphology
  • Comprised of actin filaments, intermediate filaments, and microtubules
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3
Q

Describe actin filaments

A

Also called microfilaments
7 nm in diameter

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4
Q

Describe intermediate filaments

A

Provide the scaffold
Keratins 7-12 nm diameter
Span the cytoplasm and attach at desmosomes

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5
Q

Describe microtubules

A

A and B tubulin
20 nm in diameter

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6
Q

Describe the size, charge, and solubility of keratins

A
  • Heterogenous in size (40 to 70 kDa)
  • Heterogenous in charge (4.7 to 8.4 pI)
  • All of them are insoluble
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7
Q

How many functional genes for keratins have been identified in humans?

A

54 (28 Type I and 26 Type II)

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8
Q

How well are keratins conserved in mammals?

A

Nearly perfectly

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9
Q

Where can you find high numbers of keratins?

A

Most surface exposed squamous epithelium

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10
Q

Describe the rim and spoke hypothesis

A

Keratins make a pan-cytoplasmic network from the nucleus surface to the periphery of the cytoplasm where they are membrane anchored at the sire of cell-matrix and cell-cell adhesion (ex. hemidesmosomes and desmosomes)

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11
Q

Where are keratins concentrated in polarized epithelial cells?

A

They are asymmetrically organized with keratins concentrated at the cytoplasmic periphery at the apical pole

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12
Q

Describe Type I keratins

A
  • Slightly smaller and more acidic than Type II
  • K9-19 in the epidermis
  • HA 1-8 in hair follicles/nails
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13
Q

Describe Type II keratins

A
  • Slightly larger and more basic/neutral than Type I
  • K1-8 in the epidermis
  • Hb 1-6 in the hair follicle/nail
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14
Q

What is the ratio of Type I to Type II keratins in mature intermediate filaments?

A

1:1 molar ratio so most Type I and Type II keratin genes are regulated in a pairwise, tissue type-related, and differentiation related fashion

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15
Q

Elaborate on the nomeclature of keratins (old vs new)

A
  • Original naming scheme from 1982 and listed keratins 1-19, Ha, and Hb keratins
  • Now there is a new scheme for humans that divides the genes into three categories (numbers go much higher and divide out non-human ones)
    1) epithelial keratins/genes
  • Type I is 9-28
  • Type II is 1-8 and 71-80

2) hair keratins/genes
- Type I is 31-40
- Type II is 81-86

3) keratin pseudogenes
- Type I is 221+
-Type II is 121-220

There is non-human Type I epithelial and hair which is 41-70 and Type II which is 87-120

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16
Q

Where is the mutation in curly coat/sphynx/Devon rexes?

A

Keratin 71

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17
Q

What are keratin 71 mutations associated with?

A

Wavy/curly/wooly phenotype in dogs, cats, and humans

18
Q

What are keratin 74 mutations associated with?

A

Wavy/curly/wooly phenotype in humans

19
Q

What are keratin 25 mutations associated with?

A

Wavy/curly/wooly phenotype in horses, humans, and mice

20
Q

What are keratin 27 mutations associated with?

A

Wavy/curly/wooly phenotype in cattle and mice

21
Q

What are the primary keratins associated with the stratum basale?

A

K5/K14 (also K1/K6 in dogs)

22
Q

What are the primary keratins associated with the inner root sheath of the hair shaft?

A

K71-74 and K25-28

23
Q

What are the primary keratins associated with the outer root sheath of the hair shaft?

A

K5, 6 and K14, 16, 17

24
Q

What are the primary keratins associated with the companion layer of the hair shaft?

A

K75, 76 and K16, 17

25
Q

Describe the structure of keratin (singular, not yet an intermediate filament)

A
  • Has a central rod domain (main determinant of self-assembly) that is flanked by highly variable sequences at the N-terminal head and C-terminal tail domains with glycine loops at both
  • Head and tail are cystine rich and protease accessible to allow for interactions with other molecules and post-translational modifications with disulfide bonds which allow for different functions and regulation
  • Some of the middle parts of the rod section are glycine and proline rich which confers flexibility
26
Q

Describe the formation of an intermediate filament aka polymerization

A
  • A type I and type II keratin combine to form parallel dimers (“coiled-coil”)
  • Two of these combine to form staggered, antiparallel tetramers (“protofibril”)
  • Two protofibrils combine (stacking end to end) to form a protofilament
  • Four protofibrils form a grouping that is crossed linked by disulfide bonds and is called a keratin intermediate filament
27
Q

How do hair follicle keratins organize differently than other keratin intermediate filaments?

A
  • In the hair follicle, keratins organize such that they are stretched out longitudinally (“macrofibrils”) then twist
  • Are crosslinked with keratin associated proteins (KAPs) in addition to disulfide bonds to make it stronger
28
Q

What is filaggrin?

A
  • Filament aggregating protein
  • Cationic
  • Histidine rich
  • Interacts with intermediate filaments but not other components of the cytoskeleton
  • Organizes keratin intermediate filaments into tight bundles
29
Q

What is profilaggrin?

A
  • The precursor to filaggrin
  • Giant, heavily phosphorylated, and insoluble
  • Main constituent of keratohyalin granules
  • Has filaggrin repeats (4 dogs, 10-12 in humans and 12-20 in mice) flanked by two truncated filaggrin repeats by a C-terminal and an N-terminal (that has two Ca2+ binding motifs)
  • Synthesis starts shortly after expression of K1 and K10 start
30
Q

What is filaggrin degraded into?

A

Degraded in the stratum corneum by caspase-14 –> hygroscopic free amino acids –> natural moisturizing factors pyrrolidone carboxylic acid (PCA = moisture) and urocanic acid (UCA = photoprotection)

31
Q

Which keratin promotes anagen in the hair follicle and how?

A

K17, attenuates TNF-a-induced apoptosis in matrix keratinocytes

32
Q

Which keratin regulates protein synthesis and cell size in wound-proximal keratinocytes?

A

K17

33
Q

Which keratins are primary present in the suprabasal layers?

A

K1/K10 (dogs also have K4, K15/16)
- keratin intermediate filaments are organized with more bundling when these appear

34
Q
A

Structure of keratin

35
Q

Think about the structure of keratin intermediate filaments

A
36
Q

What is the cubic rod-packing and membrane templating model?

A
  • Disputes keratin self-assembly
  • Proposes membrane template organizes keratin assembly
  • Explains strength and water-holding capacity of epidermis
  • Explains findings with cryotransmission electron microscopy on fully-hydrated epidermis
37
Q

Which Type II keratin is expressed at later stages of differentiation (ie. starting in the granular layer)?

A

K2e (and K11?)

38
Q

Which keratins are normally restricted to wound repair but may be upregulated in psoriasis and other hyperplastic disorders?

A

K6a, K6b, K16, and/or K17

39
Q

Which keratin is present in the stress bearing ridges of the palm/sole and provides a more resilient cytoskeleton?

A

Type I K9

40
Q

Which keratins have more pliability than K1, K9, and K10; function as a hinge; and are found in the secondary ridges of the human palm/sole?

A

K6a, K16, and K17

ACVD Exam (21 decks)

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