Proteomic Analysis of Loricrin Knockout Mouse Epidermis.

Area of Science:

• Dermatology
• Biochemistry
• Genetics

Background:

• The epidermal corneocyte envelope provides a scaffold for the skin's lipid barrier.
• Deficient crosslinking by keratinocyte transglutaminase (TGM1) causes congenital ichthyoses, a skin barrier disorder.
• The role of individual envelope proteins, like loricrin, in barrier function is not fully understood.

Purpose of the Study:

• To investigate the impact of loricrin deficiency on the epidermal corneocyte envelope proteome.
• To understand how the loss of loricrin affects protein incorporation into the envelope and keratin network.
• To rationalize why the absence of a single envelope component may not lead to severe barrier defects.

Main Methods:

• Proteomic analysis using mass spectrometry to compare protein profiles of loricrin knockout mice epidermis and wild-type littermates.
• Quantification of protein incorporation into the corneocyte envelope and disulfide-bonded keratin network.

Main Results:

• Approximately 40 proteins showed altered incorporation into the envelope material in loricrin knockout mice compared to wild-type.
• Nearly half of these altered proteins were also incorporated differently into the corneocyte's keratin network.
• Keratin 1, keratin 10, and loricrin are major envelope components, but dozens of other proteins are also present.

Conclusions:

• Loss of loricrin influences the incorporation of other proteins into the envelope, likely due to altered protein-protein interactions during epidermal maturation.
• The presence of numerous alternative transglutaminase substrates explains the potential formation of functional envelopes even with the loss of loricrin.
• This highlights a compensatory mechanism in skin barrier formation, rationalizing the mild phenotype observed in loricrin knockout mice.