PUBLICATION
Cellular localization of the K+ -dependent Na+ -Ca2+ exchanger NCKX5 and the role of the cytoplasmic loop in its distribution in pigmented cells
- Authors
- Rogasevskaia, T.P., Szerencsei, R.T., Jalloul, A.H., Visser, F., Winkfein, R.J., Schnetkamp, P.P.M.
- ID
- ZDB-PUB-190416-21
- Date
- 2019
- Source
- Pigment cell & melanoma research 32: 55-67 (Journal)
- Registered Authors
- Keywords
- SLC24A5, TGN, MNT1, NCKX5, Na+/Ca2+-K+ exchanger, cytoplasmic loop, pigmentation
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Autoantigens/metabolism
- Calcium/metabolism
- Cell Count
- HEK293 Cells
- Humans
- Membrane Glycoproteins/metabolism
- Membrane Proteins/metabolism
- Mice
- Mutation/genetics
- Pigmentation*/drug effects
- Potassium/pharmacology*
- Protein Structure, Secondary
- Protein Transport/drug effects
- Sodium-Calcium Exchanger/chemistry*
- Sodium-Calcium Exchanger/metabolism*
- Structure-Activity Relationship
- Zebrafish
- trans-Golgi Network/drug effects
- trans-Golgi Network/metabolism
- PubMed
- 29981211 Full text @ Pigment Cell Melanoma Res.
Citation
Rogasevskaia, T.P., Szerencsei, R.T., Jalloul, A.H., Visser, F., Winkfein, R.J., Schnetkamp, P.P.M. (2019) Cellular localization of the K+ -dependent Na+ -Ca2+ exchanger NCKX5 and the role of the cytoplasmic loop in its distribution in pigmented cells. Pigment cell & melanoma research. 32:55-67.
Abstract
NCKX5 is a bidirectional K+ -dependent Na+ -Ca2+ exchanger, which belongs to the SLC24A gene family. In particular, the A111T mutation of NCKX5 has been associated with reduced pigmentation in European populations. In contrast to other NCKX isoforms, which function in the plasma membrane (PM), NCKX5 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 NCKX5 loop deletion mutants and NCKX2-NCKX5 chimeras to address these two questions after expression in pigmented MNT1 cells. Our results show that NCKX5 is not a PM resident and is exclusively located in the TGN. Moreover, the large cytoplasmic loop is the determinant for retaining NCKX5 in the TGN.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping