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Cellular localization of the K + ‐dependent Na + –Ca 2+ exchanger NCKX 5 and the role of the cytoplasmic loop in its distribution in pigmented cells
Author(s) -
Rogasevskaia Tatiana P.,
Szerencsei Robert T.,
Jalloul Ali H.,
Visser Frank,
Winkfein Robert J.,
Schnetkamp Paul P. M.
Publication year - 2019
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12723
Subject(s) - cytoplasm , chemistry , distribution (mathematics) , anion exchanger , biophysics , ion exchange , radiochemistry , biochemistry , ion , biology , mathematical analysis , mathematics , organic chemistry
NCKX 5 is a bidirectional K + ‐dependent Na + –Ca 2+ exchanger, which belongs to the SLC 24A gene family. In particular, the A111T mutation of NCKX 5 has been associated with reduced pigmentation in European populations. In contrast to other NCKX isoforms, which function in the plasma membrane ( PM ), NCKX 5 has been shown to localize either in the trans‐Golgi network ( TGN ) or in melanosomes. Moreover, sequences responsible for retaining its intracellular localization are unknown. This study addresses two major questions: (i) clarification of intracellular location of NCKX5 and (ii) identification of sequences that retain NCKX5 inside the cell. We designed a set of cDNA constructs representing NCKX 5 loop deletion mutants and NCKX 2– NCKX 5 chimeras to address these two questions after expression in pigmented MNT 1 cells. Our results show that NCKX 5 is not a PM resident and is exclusively located in the TGN . Moreover, the large cytoplasmic loop is the determinant for retaining NCKX 5 in the TGN .