Quantitative mapping of microtubule-associated protein 2c (MAP2c) phosphorylation and regulatory protein 14-3-3 zeta-binding sites reveals key differences between MAP2c and its homolog Tau

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F17%3A00094770" target="_blank" >RIV/00216224:14740/17:00094770 - isvavai.cz</a>

Result on the web

<a href="http://www.jbc.org/content/292/16/6715" target="_blank" >http://www.jbc.org/content/292/16/6715</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.M116.771097" target="_blank" >10.1074/jbc.M116.771097</a>

Result language

angličtina

Original language name

Quantitative mapping of microtubule-associated protein 2c (MAP2c) phosphorylation and regulatory protein 14-3-3 zeta-binding sites reveals key differences between MAP2c and its homolog Tau

Original language description

Microtubule-associated protein 2c (MAP2c) is involved in neuronal development and is less characterized than its homolog Tau, which has various roles in neurodegeneration. Using NMR methods providing single-residue resolution and quantitative comparison, we investigated molecular interactions important for the regulatory roles of MAP2c in microtubule dynamics. We found that MAP2c and Tau significantly differ in the position and kinetics of sites that are phosphorylated by cAMP-dependent protein kinase (PKA), even in highly homologous regions. Wedetermined the binding sites of unphosphorylated and phosphorylated MAP2c responsible for interactions with the regulatory protein 14-3-3 zeta. Differences in phosphorylation and in charge distribution between MAP2c and Tau suggested that both MAP2c and Tau respond to the same signal (phosphorylation by PKA) but have different downstream effects, indicating a signaling branch point for controlling microtubule stability. Although the interactions of phosphorylated Tau with 14-3-3 zeta are supposed to be a major factor in microtubule destabilization, the binding of 14-3-3 zeta to MAP2c enhanced by PKA-mediated phosphorylation is likely to influence microtubule-MAP2c binding much less, in agreement with the results of our tubulin co-sedimentation measurements. The specific location of the major MAP2c phosphorylation site in a region homologous to the muscarinic receptor-binding site of Tau suggests that MAP2c also may regulate processes other than microtubule dynamics.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10600 - Biological sciences

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

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Volume of the periodical

292

Issue of the periodical within the volume

16

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

6715-6727

UT code for WoS article

000399813400023

EID of the result in the Scopus database

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