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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1782394984223211520 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4603932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sauvanetcecile thefunctionanddynamicsoftheapicalscaffoldingproteine3karpareregulatedbycellcyclephosphorylation AT garbettdamien thefunctionanddynamicsoftheapicalscaffoldingproteine3karpareregulatedbycellcyclephosphorylation AT bretscheranthony thefunctionanddynamicsoftheapicalscaffoldingproteine3karpareregulatedbycellcyclephosphorylation AT sauvanetcecile functionanddynamicsoftheapicalscaffoldingproteine3karpareregulatedbycellcyclephosphorylation AT garbettdamien functionanddynamicsoftheapicalscaffoldingproteine3karpareregulatedbycellcyclephosphorylation AT bretscheranthony functionanddynamicsoftheapicalscaffoldingproteine3karpareregulatedbycellcyclephosphorylation |