The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation

We examine the dynamics and function of the apical scaffolding protein E3KARP/NHERF2, which consists of two PDZ domains and a tail containing an ezrin-binding domain. The exchange rate of E3KARP is greatly enhanced during mitosis due to phosphorylation at Ser-303 in its tail region. Whereas E3KARP c...

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Autores principales: Sauvanet, Cécile, Garbett, Damien, Bretscher, Anthony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603932/
https://www.ncbi.nlm.nih.gov/pubmed/26310448
http://dx.doi.org/10.1091/mbc.E15-07-0498
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author Sauvanet, Cécile
Garbett, Damien
Bretscher, Anthony
author_facet Sauvanet, Cécile
Garbett, Damien
Bretscher, Anthony
author_sort Sauvanet, Cécile
collection PubMed
description We examine the dynamics and function of the apical scaffolding protein E3KARP/NHERF2, which consists of two PDZ domains and a tail containing an ezrin-binding domain. The exchange rate of E3KARP is greatly enhanced during mitosis due to phosphorylation at Ser-303 in its tail region. Whereas E3KARP can substitute for the function of the closely related scaffolding protein EBP50/NHERF1 in the formation of interphase microvilli, E3KARP S303D cannot. Moreover, the S303D mutation enhances the in vivo dynamics of the E3KARP tail alone, whereas in vitro the interaction of E3KARP with active ezrin is unaffected by S303D, implicating another factor regulating dynamics in vivo. A-Raf is found to be required for S303 phosphorylation in mitotic cells. Regulation of the dynamics of EBP50 is known to be dependent on its tail region but modulated by PDZ domain occupancy, which is not the case for E3KARP. Of interest, in both cases, the mechanisms regulating dynamics involve the tails, which are the most diverged region of the paralogues and probably evolved independently after a gene duplication event that occurred early in vertebrate evolution.
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spelling pubmed-46039322015-12-30 The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation Sauvanet, Cécile Garbett, Damien Bretscher, Anthony Mol Biol Cell Articles We examine the dynamics and function of the apical scaffolding protein E3KARP/NHERF2, which consists of two PDZ domains and a tail containing an ezrin-binding domain. The exchange rate of E3KARP is greatly enhanced during mitosis due to phosphorylation at Ser-303 in its tail region. Whereas E3KARP can substitute for the function of the closely related scaffolding protein EBP50/NHERF1 in the formation of interphase microvilli, E3KARP S303D cannot. Moreover, the S303D mutation enhances the in vivo dynamics of the E3KARP tail alone, whereas in vitro the interaction of E3KARP with active ezrin is unaffected by S303D, implicating another factor regulating dynamics in vivo. A-Raf is found to be required for S303 phosphorylation in mitotic cells. Regulation of the dynamics of EBP50 is known to be dependent on its tail region but modulated by PDZ domain occupancy, which is not the case for E3KARP. Of interest, in both cases, the mechanisms regulating dynamics involve the tails, which are the most diverged region of the paralogues and probably evolved independently after a gene duplication event that occurred early in vertebrate evolution. The American Society for Cell Biology 2015-10-15 /pmc/articles/PMC4603932/ /pubmed/26310448 http://dx.doi.org/10.1091/mbc.E15-07-0498 Text en © 2015 Sauvanet et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Sauvanet, Cécile
Garbett, Damien
Bretscher, Anthony
The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation
title The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation
title_full The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation
title_fullStr The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation
title_full_unstemmed The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation
title_short The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation
title_sort function and dynamics of the apical scaffolding protein e3karp are regulated by cell-cycle phosphorylation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603932/
https://www.ncbi.nlm.nih.gov/pubmed/26310448
http://dx.doi.org/10.1091/mbc.E15-07-0498
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