Gene mutations that inactivate the enzyme PNPLA1 cause congenital ichthyosis, a rare inherited skin disease characterized by scaly and inflamed skin. Altered PNPLA1 activity also is implicated in allergic dermatitis and other common skin diseases.
Jason Meyer, MD, PhD, and colleagues studied the enzymatic properties of PNPLA1 to explore the hypothesis that it catalyzes the synthesis of acylceramides and acyl acids that are unique to the epidermis and required for skin barrier formation.
They expressed and partially purified a truncated form of PNPLA1, a related family member (PNPLA2), and a co-activator protein, and they analyzed enzymatic products using chromatography and mass spectrometry methods (HPLC-UV and LC-MS).
In the Journal of Lipid Research, the researchers reported details of PNPLA1 activity on various substrates. The findings demonstrated a role for PNPLA1 in the synthesis of acylceramides and acyl acids in epidermis, supporting the requirement for PNPLA1 in skin barrier formation.
Meyer, instructor in Dermatology, is the first and co-corresponding author of the Journal of Lipid Research report with senior author Alan Brash, PhD. William Boeglin, senior researcher and lab manager for the Brash Laboratory, also contributed to the study. The research was supported by the National Institutes of Health (grants GM134548 and GM007569).