Phosphorylation of multiple proteins involved in ciliogenesis
by Tau Tubulin Kinase 2

J 2020

Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2

BERNATÍK, Ondřej, Petra PEJŠKOVÁ, David VYSLOUŽIL, Kateřina HANÁKOVÁ, Zbyněk ZDRÁHAL et. al.

Basic information

Original name

Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2

Authors

BERNATÍK, Ondřej (203 Czech Republic, belonging to the institution), Petra PEJŠKOVÁ (203 Czech Republic, belonging to the institution), David VYSLOUŽIL (203 Czech Republic, belonging to the institution), Kateřina HANÁKOVÁ (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution) and Lukáš ČAJÁNEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Molecular Biology of the Cell, Bethesda, The American Society for Cell Biology, 2020, 1059-1524

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.138

RIV identification code

RIV/00216224:14110/20:00114077

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1091/mbc.E19-06-0334

UT WoS

000530664800004

Keywords in English

INTRINSICALLY DISORDERED PROTEIN; PRIMARY CILIA; SUBSTRATE DETERMINANTS; MOTHER CENTRIOLE; EARLY STEPS; TTBK2; DOCKING; ATAXIA; CEP164; MUTATIONS

Abstract

V originále

Primary cilia are organelles necessary for proper implementation of developmental and homeostasis processes. To initiate their assembly, coordinated actions of multiple proteins are needed. Tau tubulin kinase 2 (TTBK2) is a key player in the cilium assembly pathway, controlling the final step of cilia initiation. The function of TTBK2 in ciliogenesis is critically dependent on its kinase activity; however, the precise mechanism of TTBK2 action has so far not been fully understood due to the very limited information about its relevant substrates. In this study, we demonstrate that CEP83, CEP89, CCDC92, Rabin8, and DVL3 are substrates of TTBK2 kinase activity. Further, we characterize a set of phosphosites of those substrates and CEP164 induced by TTBK2 in vitro and in vivo. Intriguingly, we further show that identified TTBK2 phosphosites and consensus sequence delineated from those are distinct from motifs previously assigned to TTBK2. Finally, we show that TTBK2 is also required for efficient phosphorylation of many S/T sites in CEP164 and provide evidence that TTBK2-induced phosphorylations of CEP164 modulate its function, which in turn seems relevant for the process of cilia formation. In summary, our work provides important insight into the substrates-TTBK2 kinase relationship and suggests that phosphorylation of substrates on multiple sites by TTBK2 is probably involved in the control of ciliogenesis in human cells.

Links

GA19-05244S, research and development project

Name: Molekulární aspekty ciliogeneze: zaměření na Tau Tubulin Kinázu 2

Investor: Czech Science Foundation

GJ16-03269Y, research and development project

Name: Tau tubulin kináza 2 v ciliogenezi: molekulární mechanismy a funkční důsledky

Investor: Czech Science Foundation

LM2018127, research and development project

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

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

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

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

ROZV/28/LF21/2020, interní kód MU

Name: WnUí3-kateninová dráha a ciliogeneze

Investor: Ministry of Education, Youth and Sports of the CR, Internal development projects

90127, large research infrastructures

Name: CIISB II

90129, large research infrastructures

Name: Czech-BioImaging II

Citovat

BERNATÍK, Ondřej, Petra PEJŠKOVÁ, David VYSLOUŽIL, Kateřina HANÁKOVÁ, Zbyněk ZDRÁHAL and Lukáš ČAJÁNEK. Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2. Molecular Biology of the Cell. Bethesda: The American Society for Cell Biology, 2020, vol. 31, No 10, p. 1032-1046. ISSN 1059-1524. Available from: https://dx.doi.org/10.1091/mbc.E19-06-0334.

@article{1638476,
   author = {Bernatík, Ondřej and Pejšková, Petra and Vysloužil, David and Hanáková, Kateřina and Zdráhal, Zbyněk and Čajánek, Lukáš},
   article_location = {Bethesda},
   article_number = {10},
   doi = {http://dx.doi.org/10.1091/mbc.E19-06-0334},
   keywords = {INTRINSICALLY DISORDERED PROTEIN; PRIMARY CILIA; SUBSTRATE DETERMINANTS; MOTHER CENTRIOLE; EARLY STEPS; TTBK2; DOCKING; ATAXIA; CEP164; MUTATIONS},
   language = {eng},
   issn = {1059-1524},
   journal = {Molecular Biology of the Cell},
   title = {Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2},
   url = {https://www.molbiolcell.org/doi/10.1091/mbc.E19-06-0334},
   volume = {31},
   year = {2020}
}

TY  - JOUR
ID  - 1638476
AU  - Bernatík, Ondřej - Pejšková, Petra - Vysloužil, David - Hanáková, Kateřina - Zdráhal, Zbyněk - Čajánek, Lukáš
PY  - 2020
TI  - Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2
JF  - Molecular Biology of the Cell
VL  - 31
IS  - 10
SP  - 1032-1046
EP  - 1032-1046
PB  - The American Society for Cell Biology
SN  - 10591524
KW  - INTRINSICALLY DISORDERED PROTEIN
KW  - PRIMARY CILIA
KW  - SUBSTRATE DETERMINANTS
KW  - MOTHER CENTRIOLE
KW  - EARLY STEPS
KW  - TTBK2
KW  - DOCKING
KW  - ATAXIA
KW  - CEP164
KW  - MUTATIONS
UR  - https://www.molbiolcell.org/doi/10.1091/mbc.E19-06-0334
L2  - https://www.molbiolcell.org/doi/10.1091/mbc.E19-06-0334
N2  - Primary cilia are organelles necessary for proper implementation of developmental and homeostasis processes. To initiate their assembly, coordinated actions of multiple proteins are needed. Tau tubulin kinase 2 (TTBK2) is a key player in the cilium assembly pathway, controlling the final step of cilia initiation. The function of TTBK2 in ciliogenesis is critically dependent on its kinase activity; however, the precise mechanism of TTBK2 action has so far not been fully understood due to the very limited information about its relevant substrates. In this study, we demonstrate that CEP83, CEP89, CCDC92, Rabin8, and DVL3 are substrates of TTBK2 kinase activity. Further, we characterize a set of phosphosites of those substrates and CEP164 induced by TTBK2 in vitro and in vivo. Intriguingly, we further show that identified TTBK2 phosphosites and consensus sequence delineated from those are distinct from motifs previously assigned to TTBK2. Finally, we show that TTBK2 is also required for efficient phosphorylation of many S/T sites in CEP164 and provide evidence that TTBK2-induced phosphorylations of CEP164 modulate its function, which in turn seems relevant for the process of cilia formation. In summary, our work provides important insight into the substrates-TTBK2 kinase relationship and suggests that phosphorylation of substrates on multiple sites by TTBK2 is probably involved in the control of ciliogenesis in human cells.
ER  -

BERNATÍK, Ondřej, Petra PEJŠKOVÁ, David VYSLOUŽIL, Kateřina HANÁKOVÁ, Zbyněk ZDRÁHAL and Lukáš ČAJÁNEK. Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2. \textit{Molecular Biology of the Cell}. Bethesda: The American Society for Cell Biology, 2020, vol.~31, No~10, p.~1032-1046. ISSN~1059-1524. Available from: https://dx.doi.org/10.1091/mbc.E19-06-0334.

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