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Mutations in PLC δ1 associated with hereditary leukonychia display divergent PIP 2 hydrolytic function
Author(s) -
Nomikos Michail,
Thanassoulas Angelos,
Beck Konrad,
Theodoridou Maria,
Kew Jasmine,
Kashir Junaid,
Calver Brian L.,
Matthews Emily,
Rizkallah Pierre,
Sideratou Zili,
Nounesis George,
Lai F. Anthony
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13939
Subject(s) - function (biology) , mutation , chemistry , genetics , microbiology and biotechnology , biology , gene
Hereditary leukonychia is a rare genetic nail disorder characterized by distinctive whitening of the nail plate of all 20 nails. Hereditary leukonychia may exist as an isolated feature, or in simultaneous occurrence with other cutaneous or systemic pathologies. Associations between hereditary leukonychia and mutations in the gene encoding phospholipase C delta‐1 ( PLC δ1) have previously been identified. However, the molecular mechanisms underlying PLC δ1 mutations and hereditary leukonychia remain uncharacterized. In the present study, we introduced hereditary leukonychia‐linked human PLC δ1 mutations (C209R, A574T and S740R) into equivalent residues of rat PLC δ1 (C188R, A553T and S719R), and investigated their effect on the biophysical and biochemical properties of the PLC δ1 protein. Our data suggest that these PLC δ1 mutations associated with hereditary leukonychia do not uniformly alter the enzymatic ability of this protein leading to loss/gain of function, but result in significantly divergent enzymatic properties. We demonstrate here for the first time the importance of PLC ‐mediated calcium (Ca 2+ ) signalling within the manifestation of hereditary leukonychia. PLC δ1 is almost ubiquitous in mammalian cells, which may explain why hereditary leukonychia manifests in association with other systemic pathologies relating to keratin expression.