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Keratinization Flashcards

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1
Q

What is keratinization?

A

Keratinocyte cytodifferentiation from post germinative state to fully differentiated, hardened cell, constituting a keratin containing surface layer such as stratum corneum

Genetically programmed complex series of metabolic events and morphologic changes.

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2
Q

What types of cytoplasmic filaments make up the keratinocyte cytoskeleton?

A
  • Keratin
  • Actin
  • Tubulin

Intermediate tonofilaments: Keratin (KIF), microfilaments: Actin, microtubules: A & B tubulin.

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3
Q

What are the diameters of the cytoskeletal filaments?

A
  • Keratin: 7-12 nm (intermediate)
  • Actin: 7 nm (smallest)
  • Tubulin: 20 nm (largest)

These diameters reflect their structural roles in keratinocytes.

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4
Q

What are keratins (cytokeratins)?

A

Insoluble structural proteins, heterogenous in size and charge, crucial for the epidermis

Keratin genes are highly conserved across mammals.

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5
Q

How are keratins classified?

A
  • Acidic vs. Basic
  • Soft vs. Hard
  • Alpha vs. Beta

Type 1 keratins (K9-20/40) are acidic and smaller; Type 2 (K1-8) are neutral to basic and larger.

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6
Q

What is the structure of keratin?

A

Tripartite structure with 3 domains: head, central, and tail

The head and tail domains contribute to self-assembly and stability.

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7
Q

What is filaggrin?

A

Cationic, histidine-rich enzyme that cross-links keratin intermediate filaments

Comes from inactive precursor, profilaggrin, synthesized in stratum spinosum.

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8
Q

What does profilaggrin do?

A

Contains Ca-binding domain, involved in processing and cornification

Degraded into FLG monomers which cross-link keratin intermediate filaments.

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9
Q

What are natural moisturizing factors (NMFs)?

A

Hydration and acidic pH components formed from degraded filaggrin

Examples include urocanic acid and pyrrolidone carboxylic acid.

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10
Q

True or False: Keratins play a role in signal transduction.

A

True

Keratins also impact organelle transport and barrier function.

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11
Q

What are the main functions of keratins in the skin?

A
  • Structural support
  • Enhance keratinocyte trauma resistance
  • Signal transduction

Keratins also influence melanin pigment distribution and skin pigmentation.

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12
Q

What keratins are expressed in the upper epidermis?

A

K2/K11

Suprabasilar keratinocytes express K1/K10 pairs.

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13
Q

What mutation leads to ichthyosis in Shar-pei dogs?

A

KRT1 mutation

This is an autosomal dominant condition.

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14
Q

What is the role of epidermal stem cells?

A

Cellular proliferation and terminal differentiation in the epidermis

Stem cells are organized in Epidermal Proliferative Units (EPU).

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15
Q

What happens during wound healing in keratinocytes?

A

Lateral migration of proliferating epithelium reestablishes the epithelium

This process also occurs following UV irradiation.

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16
Q

What are the stimuli that direct progenitor cells toward terminal differentiation?

A
  • Wnt/β-catenin
  • BLIMP1

These pathways help regulate the transition from basal to spinous layers.

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17
Q

What is the effect of high calcium levels in the stratum granulosum?

A

Inhibits keratinocyte proliferation and promotes differentiation

Calcium is crucial for protein synthesis and adhesion.

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18
Q

What is the role of TGFβ in keratinocytes?

A

Suppresses DNA synthesis and mitosis

It is important for immunological tolerance and is normally present in low levels in the upper epidermis.

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19
Q

What is the epidermal differentiation complex?

A

A complex on chromosome 1q21 that encodes for various keratins and proteins

It plays a critical role in skin development.

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20
Q

What is the function of the SERCA2 pump?

A

Restores Ca supplies in the endoplasmic reticulum

SERCA2 is essential for regulating intracellular calcium levels.

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21
Q

What condition is associated with ATP2A2 mutation?

A

Darier’s disease

This mutation affects calcium homeostasis in keratinocytes.

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22
Q

What is the role of the SPCA1 pump?

A

Functions in the Golgi apparatus to regulate calcium similar to SERCA1

SPCA1 is involved in calcium transport within the cell.

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23
Q

What disease is linked to ATP2A2 mutation in humans?

A

Hailey-Hailey disease

This condition is characterized by skin fragility and recurrent blisters.

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24
Q

What is the epidermal differentiation complex?

A

A genomic region on chromosome 1q21 that encodes proteins for terminal differentiation

Key proteins include involucrin and loricrin.

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25
Define terminal differentiation.
Programmed cell death ## Footnote This process is crucial for the formation of the outer epidermal layers.
26
What are the key defining characteristics of each epidermal layer?
Position, shape, polarity, morphology, state of differentiation ## Footnote These characteristics help classify the distinct layers of the epidermis.
27
What are desmosomes?
Cell-cell adhesion structures in all layers of the epidermis ## Footnote They are crucial for maintaining structural integrity.
28
What cytoskeletal component is associated with desmosomes?
Keratins ## Footnote Keratins provide strength and stability to the desmosomal connections.
29
List the plaque proteins involved in desmosomal adhesion.
* Plakoglobin * Desmoplakin * Desmocalmin * Plakophilin ## Footnote These proteins link the cytoskeleton to the desmosomal cadherins.
30
What are adherens junctions?
Cell-cell adhesion structures located beneath tight junctions ## Footnote They are important for maintaining cellular integrity and signaling.
31
What is the role of tight junctions?
Create impermeable barriers in the stratum granulosum ## Footnote They seal the apical border and maintain cellular polarity.
32
What is the primary function of gap junctions?
Intercellular routes of chemical communication ## Footnote They allow transfer of ions and small molecules between adjacent keratinocytes.
33
What is the significance of calcium in keratinocyte differentiation?
Calcium levels rise to promote differentiation and protein synthesis ## Footnote This is a key signaling event during the transition from the stratum spinosum to the stratum granulosum.
34
What are lamellar bodies?
Organelles that contain lipids, proteins, and enzymes for forming the cornified lipid envelope ## Footnote They play a crucial role in skin barrier function.
35
What is the composition of the corneocyte?
Anuclear, densely packed core of keratin and filaggrin ## Footnote Corneocytes are the primary structural unit of the stratum corneum.
36
What is the purpose of the cornified envelope (CE)?
Durable, proteinaceous coating surrounding the keratin core ## Footnote The CE contributes to the skin's barrier function.
37
Which gene family is associated with desmosomal plaque proteins?
Plakins ## Footnote This family includes desmoplakins, which link plaque proteins to keratin intermediate filaments.
38
What is the function of filaggrin?
Packs keratin intermediate filaments into macrofilaments ## Footnote Filaggrin is crucial for the structural integrity of the stratum corneum.
39
What is the function of involucrin in the epidermis?
Acts as a precursor to the cornified envelope ## Footnote It is cross-linked to form the structure that protects against environmental damage.
40
What is the role of loricrin?
Provides structural support to the cornified envelope ## Footnote It is a major component of the CE and contributes to skin barrier function.
41
What is the primary function of the stratum granulosum?
Keratohyalin granules facilitate keratin assembly and barrier formation ## Footnote This layer is crucial for the transition to the outermost skin layer.
42
Which layer of the epidermis is the thickest?
Stratum spinosum ## Footnote This layer varies in thickness depending on the body region and species.
43
What is the stratum lucidum?
A thin, clear layer of dead cells found in specific locations ## Footnote It is primarily found in areas like footpads and the nasal planum.
44
What is the primary component of the stratum corneum?
Flattened, anuclear corneocytes surrounded by an extracellular lipid matrix ## Footnote This structure forms the main barrier against environmental damage.
45
What is the Cornified Envelope (CE)?
Durable, proteinaceous coating that surrounds the keratin core ## Footnote Key components include loricrin, involucrin, and keratins.
46
What is the primary mass component of the Cornified Envelope?
Loricrin (70-80% mass) ## Footnote Other components include involucrin, small protein-rich proteins, and keratins.
47
What is the role of the 'mortar' in the stratum corneum?
Lipid extracellular matrix ## Footnote It helps in the structural integrity and function of the skin barrier.
48
What does the Corneocyte Lipid Envelope (CLE) do?
Surrounds the proteinaceous CE and acts as a scaffold for intercellular lipid lamellae ## Footnote Key lipid components include omega-hydroxyceramides.
49
What are the main components of intercellular lipid lamellae?
* Ceramides (50%) * Cholesterol (25%) * Free fatty acids (15%) ## Footnote These components are essential for the barrier function of the skin.
50
What proteins are unique to the stratum corneum?
* Involucrin * Loricrin * Desmosomal proteins (envoplakin & periplakin) * Small proline-rich proteins (SPRPs) ## Footnote These proteins play significant roles in the structure and function of the skin barrier.
51
What happens to desmosomes in the stratum corneum?
They are converted to corneodesmosomes ## Footnote This conversion is crucial for the adhesion properties of the stratum corneum.
52
What is corneodesmosin (CDSN)?
A protein with high serine and glycine content that binds to desmoglea ## Footnote It is synthesized in the granular layer and plays a key role in cell adhesion.
53
What enzymes are involved in the construction of the Cornified Envelope?
* Transglutaminases (Ca-dependent) ## Footnote These enzymes cross-link various proteins to reinforce the CE.
54
What are Natural Moisturizing Factors (NMFs) derived from?
Filaggrin degradation products ## Footnote Important NMFs include urocanic acid and pyrrolidone carboxylic acid.
55
What is the permeability barrier of the stratum corneum composed of?
Corneocytes and lamellar bilayers made of hydrophobic lipids ## Footnote This barrier prevents water loss and protects against external factors.
56
What promotes desquamation in the stratum corneum?
Kallikreins (KLKs) that cleave corneodesmosomes ## Footnote They are serine proteases active at acidic pH.
57
What inhibits the activity of kallikreins?
LEKTI type 5 serine protease inhibitors ## Footnote LEKTI is secreted from lamellar bodies and inhibits desquamation.
58
What factors promote desquamation?
* Low/acidic pH * Low calcium * Increased NMF * Decreased water ## Footnote These factors optimize the function of KLKs.
59
What is the role of serine proteases in the stratum corneum?
They facilitate desquamation by cleaving corneodesmosomes ## Footnote This process is essential for shedding dead skin cells.
60
What is the significance of the differential distribution of corneodesmosomes during desquamation?
It partially accounts for the basketweave appearance on histopathology ## Footnote This appearance can also be an artifact.
61
What inhibits desquamation?
* LEKTI * Neutral pH * Cholesterol sulfate ## Footnote These factors contribute to the maintenance of the stratum corneum.

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