Epidermal Barrier Flashcards
What is a cysteine-rich highly flexible protein with glycine loops that forms the major structural component of the cornified envelope?
loricrin
What are the components of the lamellar granules/bodies?
extracellular lipids (phospholipids, glucosylceramides, spingomyelin, cholesterol), enzymes and their inhibitors (lipid hydrolases such as beta-glucocerebrosidase, acidic sphingomyelinase, secretory phospholipase A2, serine and cysteine proteases, kallikreins, cathepsins); corneodesmosin, steroid sulfatase, antimicrobial peptides (beta-defensin 2 and cathelicidin LL-37)
What protease is required for filaggrin degradation?
capsase-14
What are type II keratins?
basic to neutral, larger and include K1-8 in epidermis
Where are functional tight junctions located in the epidermis?
stratum granulosum
Epidermal tight junctions are composed of 2 families of transmembrane molecules. What are they?
claudins and occludins
What do the corneodesmosomes contain?
desmoglein 1, desmocollin 1, corneodesmosin
The epidermis can syntheize saturated and monounsaturated fatty acids but not what fatty acids?
omega-6 polyunsaturated essential fatty acids (EFAs) such as linoleic acid and alpha-linolenic acid
What is a calcium dependent family of enzymes that catalyzes the formation of N(e)-(y-glutamyl)-lysine isopeptide bonds?
transglutaminases
What proteins from the plakin protein family are present in the desmosomes?
desmoplakin, envoplakin, and periplakin
Describe keratin intermediate filament assembly
type I and type II keratin molecules form coiled-coil heterodimers –> align in antiparallel and staggered pattern to form double coiled-coil tetramers –> assemble end-to-end to form protofilaments –> assemble laterally into protofibrils –> associate into intermediate filaments
As the cornified envelope is formed, what proteins are expressed at the desmosomal plaques?
envoplakin and periplakin
What are type I keratins?
acidic, smaller, K9-19 in epidermis
What enzymes are involved in desquamation?
kallikreins and cathepsins
What are the rate limiting enzymes in free fatty synthesis?
acetyl-CoA carboxylase and fatty acid synthase
What is the primary signal for inducing lamellar granule secretion?
increase in extracellular calcium concentration in the granular layer
Describe the calcium gradient in the layers of the epidermis
Ca2+ levels are low in the basal and spinous layers –> increase towards the stratum granulosum –> decrease in the stratum corneum
What composes the corneocyte lipid envelope?
omega-hydroxyceramides
What is the structure of keratin proteins?
central alpha-helical rod domain, amino-terminal head, carboxy-terminal tail
T/F: Cholesterol must be obtained from the diet.
False - synthesized from acetate in the lower epidermis
What is a highly soluble glutamine-rich protein that forms a scaffold for the attachment of other components of the cornified envelope (connects corneocytes to extracellular lipid layer)?
involucrin
Where is profilaggrin cleaved into filaggrin (what cell layer)?
transition from granular to cornified layers
What is the rate-limiting step in cholesterol synthesis?
hydroxymethylglutaryl CoA reductase
What are adherens junctions?
cadherin-based junctions that link the actin cytoskeleton to the plasma membrane
Desquamation involves enzymatic cleavage of what attachment between corneocytes?
corneodesmosomes
What are the primary components of the keratohyalin granules?
profilaggrin, loricrin, keratin filaments
What is the action of phospholipase in development of the cornified envelope?
cleaves phospholipids into free fatty acids and glycerol
