Melanocyte Basic Science Flashcards
Where can melanoma and pigmented lesions be detected?
Skin hair, the uveal tract of eye (choroid, iris, ciliary body), leptomeninges, and inner ear (striae vascularis of cochlea
In what disease does leptomeningeal melanoma become an important risk?
Giant congenital nevus
What produces the KIT ligand?
Dermamyotome
What melanomas are c-KIT mutations associated with?
Acral, photodamaged, and mucosal melanoma; mastocytosis (HIGH YIELD)
What is the main transcription factor involved in melanogensis?
MITF
What activiates MITF?
KIT ligand, WNT, MSH, ET3
What are the downstream effects of MITF
Melanocyte survival (CDKN2A, CDK2, BCL-2), melanogenesis, melanocyte differentiation, melanocyte proliferation, melanocyte survival
Are melanocytes connected via desmosomes to keratinocytes?
NO they are “free floating”
What is the ratio of melanocytes to keratinocytes in the epidermal melanin unit?
1 melanocyte in contact with 36 keratinocytes
What is different about the pigment in the epithelium of the retina?
Melanocytes don’t act in the same way as other tissues, don’t give melanin in the same way
What organelle type are melanosomes?
Specialized types of lysosomes
What are the 4 stages of melanosomes?
I: spherical, no melanin
II-III: oval + melaning and high tyrosinase activty
IV: oval, heavy melanin depositis, minimal tyrosinase activity
What are the 2 types of melanin?
Pheomelanin or eumelanin
What pigment colors are associated w/ the 2 types of melanin and why?
- Pheomelanin: yellow to red pigment (mutant MC1R and non-functional)
- Eumelanin: brown to black pigment
What acts on MC1R?
MSH and ACTH
What is the order of binding for MC1R
Msh-alpha, acth>msh beta
What is the difference in melanosomes between light skin vs darker skin?
Melanosome types (size and transfer). Darker skin has larger melanosomes and individual organelles are transferred vs membrane-bound clusters in lighter skin types
Chronic sun exposure results in what changes in melanin?
increased melanosome size, augment anterograde transport of melansomes via kinesin activity
What protein regulates the survival and migration of melanoblasts and melanocytes during embryogenesis?
c-kit
What is the mutation involved in piebaldism?
Heterozygous germline KIT inactivating mutation
What enzymes is melanin production dependent on?
Cu-dependent enzyme, tryosinase