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Dermatology
Melanocyte Biology
Built from Dermatology, 5th Edition
What’s inside
4 sections · 124 slides
Overview
- What melanocyte biology explains
- Roadmap
- OCA1: the classic teaching example
- The same genes shape normal pigment too
- Inherited disorders of diffuse pigment dilution
- Oculocutaneous albinism (OCA) [~40% of patients have OCA1 and ~50% have OCA2]
- OCA1A
- OCA1B
- OCA2
- OCA3
- OCA4
- OCA5
- OCA6
- OCA7
- OCA8
- Hermansky–Pudlak syndrome (HPS)
- HPS1
- HPS2
- HPS3
- HPS4
- HPS5
- HPS6
- HPS7
- HPS8
- HPS9
- HPS10
- HPS11
- Chédiak–Higashi syndrome
- Entry 24
- Griscelli syndrome
- GS1
- GS2
- GS3
- GS3
Origin and Function of the Melanocyte
Where melanocytes come from, how they migrate, and where they settle in the body
- The melanocyte is a neural crest cell
- Where melanocytes migrate to
- Melanocyte migration from the neural crest
- Why melanocyte migration matters clinically
- Waardenburg syndrome: a classic neurocristopathy
- KIT receptor and KIT ligand guide migration
- Activation of the KIT receptor on melanocytes
- Endothelin signaling in melanoblast migration
- Receptor-ligand interactions in melanocyte precursors
- Transcription factors direct melanocyte development
- Signal transduction pathways and transcription factors in melanocyte differentiation
- Dermal melanocytes during development
- Gene mutations linked to dermal melanocyte lesions
- Melanocytes of the hair follicle
- Hair follicle melanocytes and vitiligo repigmentation
- Melanocytes reach the fetal epidermis early
- The epidermal melanin unit
- Melanocyte density varies by body site
- DOPA-stained epidermal sheet
- Skin color depends on activity, not cell count
Formation and Function of the Melanosome
The organelle that makes, matures, and ships out melanin
- What is a melanosome?
- Two types of melanosome cargo
- Misfolded proteins get destroyed: OCA1 and OCA3
- Pathophysiology of oculocutaneous albinism type 1 (OCA1)
- Proteins need sugar tags and correct routing
- Hermansky-Pudlak syndrome: a trafficking disorder
- Hermansky-Pudlak syndrome and melanosomal protein trafficking
- Four stages of melanosome maturation
- Four major stages of eumelanin melanosomes
- Melanosomes travel into the dendrites
- Movement of melanosomes within melanocyte dendrites
- Handoff to keratinocytes: the transfer step
- Griscelli syndrome: when transfer fails
- Other causes of impaired melanosome transfer
- Light skin versus dark skin: it's about melanosomes
- Predominant melanosome stage by pigmentation level
- Variation of predominant melanosomal stages with level of cutaneous pigmentation.
- Melanosomes in lightly versus darkly pigmented skin
- Dark skin melanosomes persist longer
Regulation of Melanin Biosynthesis
The enzyme pathway and hormone signals that set pigment type and amount
- The melanin pathway starts with tyrosine
- The melanin biosynthetic pathway
- Eumelanin versus pheomelanin
- Two outcomes of the same enzyme step
- What controls tyrosinase activity
- Phenylketonuria and pigment dilution
- Copper and pigment: tyrosinase's hidden requirement
- Beyond tyrosinase: more control points
- The P protein and OCA2
- The P protein within the melanosome membrane
- Melanin's job: camouflage and sun protection
- POMC: one gene, many hormone products
- Post-translational processing of the POMC polypeptide
- POMC mutations and receptor mutations
- MC1R-targeted drugs
- Five melanocortin receptors
- Major forms of the melanocortin receptor (MCR).
- MC1R within the melanocyte plasma membrane
- How MC1R signals inside the cell
- The MC1R signaling cascade
- Activation of a G-protein-coupled receptor such as MC1R
- When MC1R signaling is weak
- Agouti protein: MC1R's built-in brake
- MSH and agouti protein interactions with MC1R
- The agouti coat pattern
- Formation of the agouti hair pattern
- McCune-Albright syndrome: a stuck 'on' switch
- Other signals that raise pigment production
- Inflammation can also switch pigment
- Genes behind normal pigment variation
- ASIP variants and skin tone
- Genes associated with physiologic variation in human pigmentation
- Why hair turns gray
- UV light increases melanocyte activity
- Two kinds of UV tanning response
- How UV switches on more pigment
- More UV pigment-switching mechanisms
- Mechanisms of UVR-induced pigmentation
- Red hair, UV damage, and skin cancer risk
- Key takeaways
- Key takeaways, continued
- References
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- References
- Dermatology, 5th Edition (2-Volume Set)