Interactions between FATP4 and ichthyin in epidermal lipid processing may provide clues to the pathogenesis of autosomal recessive congenital ichthyosis.

[aniridia]

Autosomal recessive congenital ichthyosis (ARCI ) is caused by mutations in â‰¥10 different genes , of which transglutaminase-1 (TGM 1 ) predominates . A rare form is ichthyosis prematurity syndrome (IPS ) caused by mutations in SLC 27 A 4 encoding fatty acid transporter protein 4 (FATP 4 ), believed to be an acyl-CoA synthetase activating long - and very -long -chain FA . Another ARCI is caused by mutations in NIPAL 4 , coding for ichthyin , which is proposed to be a magnesium transporter or a trans-membrane receptor . A possible interaction between FATP 4 and ichthyin has not been studied before .To find common denominators in the pathogenesis of ARCI .FATP 4 and ichthyin were analyzed by immunofluorescence and proximity ligation assay (PLA ) in healthy and ARCI patient skin and in in vitro models of ARCI epidermis .Both proteins were expressed in the upper stratum granulosum of normal epidermis and PLA confirmed a close interaction between FATP 4 and ichthyin . In IPS skin lacking FATP 4 we found reduced ichthyin expression and this finding could be reproduced in organotypic epidermis with siRNA silenced SLC 27 A 4 . In contrast , increased FATP 4 staining was found in patients with ichthyin (NIPAL 4 ) mutations and in organotypic epidermis with silenced NIPAL 4 . In patients with TGM 1 mutations , the expression of both FATP 4 and ichthyin was increased , but the PLA signal was low probably indicating a malfunctioning protein interaction .Our study suggests that FATP 4 , ichthyin and TGM 1 interact in lipid processing essential for maintaining the epidermal barrier function . It is also hypothesized that ichthyin serves as Mg (2 +)-transporter for FATP 4 in this process .

Diseases
Validation

Diseases presenting "mutations in nipal4" symptom

aniridia

lamellar ichthyosis

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