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Dermatology
Biology of Keratinocytes
Built from Dermatology, 5th Edition
What’s inside
8 sections · 93 slides
Overview
- What this topic covers
The Epidermis: Structure and Function
How the outer skin layer renews itself and builds a barrier
- What the epidermis does
- Self-renewal of the epidermis
- Moving up and out
- The four layers of the epidermis
- Epidermal differentiation across the layers
- The cornified cell envelope
- Building the cornified cell envelope
- Formation of the cornified cell envelope
- Transglutaminases: welding the envelope shut
- Transglutaminase catalysis of protein cross-links
- When transglutaminase 1 fails
- The stratum corneum as a water barrier
- A surprising finding in knockout mice
Keratin Intermediate Filaments
The tough internal fibers that give keratinocytes their strength
- What keratins are
- Intermediate filaments beyond keratin
- Types of intermediate filaments
- Classifying the keratin gene family
- Keratins always pair up
- Assembly of keratin filaments
- Structure of a keratin protein
- Hot spots for keratin mutations
- Where keratin mutations sit, and the diseases they cause
- Head and tail regions
- Keratins do more than hold cells together
- The hair follicle: a layered structure
- Hair keratin expression pattern
- Which keratins go where in hair
Epidermal Differentiation
The gene programs that turn a dividing cell into a dead, protective one
- Keratins switch as cells mature
- Cytokeratin expression across keratin types
- Keratins with a special anatomic address
- Regulatory pathways shaping differentiation
- p63: master gene of the basal layer
- What p63 controls in basal cells
- From basal cell to spinous cell
- Notch signaling and the spinous layer
- A calcium gradient drives differentiation
- Calcium-responsive proteins
- The calcium-sensing receptor
- Building the epidermis before birth
- What happens if this step fails
Keratinocyte Adhesion
The junctions that rivet keratinocytes together and hold the skin intact
- Desmosomes: cell-cell rivets
- Molecular organization of the desmosome
- What a desmosome is made of
- Linking desmosomes to the keratin skeleton
- Many genes, many combinations
- Cell junctions of the keratinocyte
- Desmosomes loosen up to let cells move
- Desmosomes as signaling centers
- Plakoglobin's dual role
- When desmosomes fail
- Two ways to lose a desmosome
- Pemphigus vulgaris and foliaceus
- Desmosomes and the heart
- Adherens junctions
- Cadherins during hair follicle formation
- Tight junctions
Keratinocyte-Matrix Interactions
How the epidermis attaches to the basement membrane below it
- The basement membrane and integrins
- A family of matrix receptors
- Keratinocyte integrin receptors
- Keratinocyte integrin receptors (continued)
- Fras1, Frem1, and Frem2
- Fraser syndrome
Related Diseases
Inherited disorders caused by failures of keratin, desmosome, or filaggrin biology
- How keratin mutations cause disease
- Epidermolysis bullosa simplex (EBS)
- Mutation location predicts severity
- Keratin disorders across many tissues
- Types of keratin mutations in mucocutaneous disorders
- Types of keratin mutations in mucocutaneous disorders (continued)
- Types of keratin mutations in mucocutaneous disorders (continued)
- Keratin mutations and pigment change
- Epidermolytic ichthyosis
- EI with and without palm/sole disease
- A mosaic form of EI
- White sponge nevus
- Keratin mutations outside the skin
- Filaggrin: what it is
- Filaggrin gene structure and mutation sites
- Ichthyosis vulgaris
- Filaggrin, eczema, and asthma
- Why mouse models matter
- Mouse models of structural and desmosomal disease
- Mouse models for structural and desmosomal proteins
- Mouse models for structural and desmosomal proteins (continued)
- Where the field is heading
- Key takeaways: structure and keratins
- Key takeaways: adhesion and disease
References
Sources cited in this chapter
- References
- References (continued)
- References (continued)
- References (continued)
- References (continued)
- Dermatology, 5th Edition (2-Volume Set)