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Formation of the cornified envelope
Stable Identifier
R-HSA-6809371
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Developmental Biology (Homo sapiens)
Keratinization (Homo sapiens)
Formation of the cornified envelope (Homo sapiens)
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As keratinocytes progress towards the upper epidermis, they undergo a unique process of cell death termed cornification (Eckhart et al. 2013). This involves the crosslinking of keratinocyte proteins such as loricrin and involucrin by transglutaminases and the breakdown of the nucleus and other organelles by intracellular and secreted proteases (Eckhart et al. 2000, Denecker et al. 2008). This process is strictly regulated by the Ca2+ concentration gradient in the epidermis (Esholtz et al. 2014). Loricrin and involucrin are encoded in ‘Epidermal Differentiation Complex’ linked to a large number of genes encoding nonredundant components of the CE (Kypriotou et al. 2012, Niehues et al. 2016). Keratinocytes produce specialized proteins and lipids which are used to construct the cornified envelope (CE), a heavily crosslinked submembranous layer that confers rigidity to the upper epidermis, allows keratin filaments to attach to any location in the cell membrane (Kirfel et al. 2003) and acts as a water-impermeable barrier. The CE has two functional parts: covalently cross-linked proteins (10 nm thick) that comprise the backbone of the envelope and covalently linked lipids (5 nm thick) that coat the exterior (Eckert et al. 2005). Desmosomal components are crosslinked to the CE to form corneodesmosomes, which bind cornified cells together (Ishida-Yamamoto et al. 2011). Mature terminally differentiated cornified cells consist mostly of keratin filaments covalently attached to the CE embedded in lipid lamellae (Kalinin et al. 2002). The exact composition of the cornified envelope varies between epithelia (Steinert et al. 1998); the relative amino-acid composition of the proteins used may determine differential mechanical properties (Kartasova et al. 1996).
Literature References
PubMed ID
Title
Journal
Year
15803139
The cornified envelope: a model of cell death in the skin
Candi, E
,
Melino, G
,
Schmidt, R
Nat. Rev. Mol. Cell Biol.
2005
Participants
Events
Envoplakin binds periplakin
(Homo sapiens)
EVL:PPL heterodimer binds the inner surface of the plasma membrane
(Homo sapiens)
TGM1 and involucrin bind the plasma membrane
(Homo sapiens)
Envoplakin, periplakin, involucrin, SPR binding mediated by TGM1 crosslinking
(Homo sapiens)
Membrane proteases cleave Profilaggrin producing Filaggrin
(Homo sapiens)
Cytoplasmic proteases cleave Profilaggrin producing Filaggrin
(Homo sapiens)
Filaggrin binds Keratin tonofilament:Desmosome
(Homo sapiens)
Fillagrin and keratin intermediate filaments polymerize forming a network
(Homo sapiens)
Reinforcement of the Cornified Envelope
(Homo sapiens)
Lamellar bodies bind the early cornified envelope
(Homo sapiens)
CDSN binds the cornified envelope
(Homo sapiens)
Late envelope proteins bind cornified envelope:CDSN
(Homo sapiens)
CASP14 cleaves filaggrin
(Homo sapiens)
Plasma membrane resorption
(Homo sapiens)
PERP binds desmosomes
(Homo sapiens)
Kazrin binds periplakin
(Homo sapiens)
ST14 hydrolyzes and activates KLK5
(Homo sapiens)
SPINK5(490-624) binds KLK5
(Homo sapiens)
Dissociation of the SPINK5:KLK5 complex at low pH
(Homo sapiens)
KLK5 cleaves and activates CELA2
(Homo sapiens)
KLK5 cleaves and activates KLK8
(Homo sapiens)
SPINK6 binds KLK12
(Homo sapiens)
SPINK6 binds KLK13
(Homo sapiens)
SPINK6 binds KLK14
(Homo sapiens)
SPINK6 binds KLK5
(Homo sapiens)
SPINK9 binds KLK5
(Homo sapiens)
LIPs hydrolyse TG to DAG and RCOOH
(Homo sapiens)
Participates
as an event of
Keratinization (Homo sapiens)
Event Information
Go Biological Process
cornification (0070268)
Orthologous Events
Formation of the cornified envelope (Bos taurus)
Formation of the cornified envelope (Caenorhabditis elegans)
Formation of the cornified envelope (Canis familiaris)
Formation of the cornified envelope (Danio rerio)
Formation of the cornified envelope (Dictyostelium discoideum)
Formation of the cornified envelope (Gallus gallus)
Formation of the cornified envelope (Mus musculus)
Formation of the cornified envelope (Plasmodium falciparum)
Formation of the cornified envelope (Rattus norvegicus)
Formation of the cornified envelope (Saccharomyces cerevisiae)
Formation of the cornified envelope (Schizosaccharomyces pombe)
Formation of the cornified envelope (Sus scrofa)
Formation of the cornified envelope (Xenopus tropicalis)
Authored
Jupe, S (2016-03-10)
Reviewed
Blumenberg, M (2016-08-12)
Created
Jupe, S (2015-11-11)
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