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14-3-3ζ escorts CCTα for calcium-activated nuclear import in lung epithelia
Journal article   Open access   Peer reviewed

14-3-3ζ escorts CCTα for calcium-activated nuclear import in lung epithelia

Marianna Agassandian, Bill B Chen, Christopher C Schuster, Jon C. D Houtman and Rama K Mallampalli
The FASEB journal, Vol.24(4), pp.1271-1283
04/2010
DOI: 10.1096/fj.09-136044
PMCID: PMC2845428
PMID: 20007511
url
https://doi.org/10.1096/fj.09-136044View
Published (Version of record) Open Access

Abstract

Integrity of animal biomembranes is critical to preserve normal cellular functions and viability. Phosphatidylcholine, an indispensible membrane component, requires the enzyme CCTα for its biosynthesis. Nuclear expression of CCTα is needed for expansion of the nuclear membrane network, but mechanisms for CCTα nuclear import are unknown. Herein, we show that in epithelia, extracellular Ca 2+ triggers CCTα cytoplasmic-nuclear translocation. CCTα nuclear import was associated with binding to 14-3-3ζ, a key regulator of protein trafficking. 14-3-3ζ was both sufficient and required for CCTα nuclear import. Helix G within the 14-3-3ζ binding groove interacts with a putative molecular signature within the CCTα carboxyl-terminal phosphoserine motif (residues 328–343). 14-3-3ζ was critically involved in preserving phosphatidylcholine synthesis and cell viability in a model of Pseudomonas aeruginosa infection where Ca 2+ concentrations increase within epithelia. Thus, 14-3-3ζ controls CCTα nuclear import in response to calcium signals, thereby regulating mammalian phospholipid synthesis. Agassandian, M., Chen, B. B., Schuster, C. C., Houtman, J. C. D., Mallampalli, R. K. 14-3-3ζ escorts CCTα for calcium-activated nuclear import in lung epithelia.
homeostasis Research Communications membrane lipid

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