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

J 2017

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

JANSEN, Séverine, Kateřina MELKOVÁ, Zuzana TROŠANOVÁ, Kateřina HANÁKOVÁ, Milan ZACHRDLA et. al.

Basic information

Original 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

Authors

JANSEN, Séverine (250 France, belonging to the institution), Kateřina MELKOVÁ (203 Czech Republic, belonging to the institution), Zuzana TROŠANOVÁ (703 Slovakia, belonging to the institution), Kateřina HANÁKOVÁ (203 Czech Republic, belonging to the institution), Milan ZACHRDLA (203 Czech Republic, belonging to the institution), Jiří NOVÁČEK (203 Czech Republic, belonging to the institution), Erik ŽUPA (703 Slovakia, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution), Jozef HRITZ (703 Slovakia, belonging to the institution) and Lukáš ŽÍDEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. Biol. 2017, 0021-9258

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.011

RIV identification code

RIV/00216224:14740/17:00094770

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1074/jbc.M116.771097

UT WoS

000399813400023

Keywords in English

INTRINSICALLY UNSTRUCTURED PROTEINS; PAIRED HELICAL FILAMENTS; TUBULIN POLYMERIZATION; MULTIDIMENSIONAL NMR; NEURONAL DEVELOPMENT; DISORDERED PROTEINS; SYNAPTIC PLASTICITY; BETA-STRUCTURE; KINASE-A; BINDING

Abstract

V originále

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.

Links

GA15-14974S, research and development project

Name: Charakterizace proteinu MAP2c (microtubule associated protein 2c) a modifikací regulujících jeho funkci s atomovým rozlišením

Investor: Czech Science Foundation

LM2015043, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

JANSEN, Séverine, Kateřina MELKOVÁ, Zuzana TROŠANOVÁ, Kateřina HANÁKOVÁ, Milan ZACHRDLA, Jiří NOVÁČEK, Erik ŽUPA, Zbyněk ZDRÁHAL, Jozef HRITZ and Lukáš ŽÍDEK. 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. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2017, vol. 292, No 16, p. 6715-6727. ISSN 0021-9258. Available from: https://dx.doi.org/10.1074/jbc.M116.771097.

@article{1381982,
   author = {Jansen, Séverine and Melková, Kateřina and Trošanová, Zuzana and Hanáková, Kateřina and Zachrdla, Milan and Nováček, Jiří and Župa, Erik and Zdráhal, Zbyněk and Hritz, Jozef and Žídek, Lukáš},
   article_location = {Bethesda, USA},
   article_number = {16},
   doi = {http://dx.doi.org/10.1074/jbc.M116.771097},
   keywords = {INTRINSICALLY UNSTRUCTURED PROTEINS; PAIRED HELICAL FILAMENTS; TUBULIN POLYMERIZATION; MULTIDIMENSIONAL NMR; NEURONAL DEVELOPMENT; DISORDERED PROTEINS; SYNAPTIC PLASTICITY; BETA-STRUCTURE; KINASE-A; BINDING},
   language = {eng},
   issn = {0021-9258},
   journal = {Journal of Biological Chemistry},
   title = {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},
   url = {http://www.jbc.org/content/292/16/6715},
   volume = {292},
   year = {2017}
}

TY  - JOUR
ID  - 1381982
AU  - Jansen, Séverine - Melková, Kateřina - Trošanová, Zuzana - Hanáková, Kateřina - Zachrdla, Milan - Nováček, Jiří - Župa, Erik - Zdráhal, Zbyněk - Hritz, Jozef - Žídek, Lukáš
PY  - 2017
TI  - 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
JF  - Journal of Biological Chemistry
VL  - 292
IS  - 16
SP  - 6715-6727
EP  - 6715-6727
PB  - Amer. Soc. Biochem. Mol. Biol.
SN  - 00219258
KW  - INTRINSICALLY UNSTRUCTURED PROTEINS
KW  - PAIRED HELICAL FILAMENTS
KW  - TUBULIN POLYMERIZATION
KW  - MULTIDIMENSIONAL NMR
KW  - NEURONAL DEVELOPMENT
KW  - DISORDERED PROTEINS
KW  - SYNAPTIC PLASTICITY
KW  - BETA-STRUCTURE
KW  - KINASE-A
KW  - BINDING
UR  - http://www.jbc.org/content/292/16/6715
L2  - http://www.jbc.org/content/292/16/6715
N2  - 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.
ER  -

JANSEN, Séverine, Kateřina MELKOVÁ, Zuzana TROŠANOVÁ, Kateřina HANÁKOVÁ, Milan ZACHRDLA, Jiří NOVÁČEK, Erik ŽUPA, Zbyněk ZDRÁHAL, Jozef HRITZ and Lukáš ŽÍDEK. 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. \textit{Journal of Biological Chemistry}. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2017, vol.~292, No~16, p.~6715-6727. ISSN~0021-9258. Available from: https://dx.doi.org/10.1074/jbc.M116.771097.

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