Molecular mechanisms underlying the role of the centriolar
CEP164-TTBK2 complex in ciliopathies

J 2022

Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies

SILVA, Ivan Rosa e, Lucia BINÓ, Christopher M. JOHNSON, Trevor J. RUTHERFORD, David NEUHAUS et. al.

Basic information

Original name

Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies

Authors

SILVA, Ivan Rosa e, Lucia BINÓ, Christopher M. JOHNSON, Trevor J. RUTHERFORD, David NEUHAUS, Antonina ANDREEVA, Lukáš ČAJÁNEK (203 Czech Republic, belonging to the institution) and Mark van BREUGEL

Edition

Structure, Cambridge, Cell Press, 2022, 0969-2126

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: 5.700

RIV identification code

RIV/00216224:14110/22:00125148

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.str.2021.08.007

UT WoS

000742422300013

Keywords in English

CEP164; TTBK2; ciliaciliogenesis; ciliopathy; nephronophthisis; basal body; centriole; distal appendage; centrosome

Abstract

V originále

Cilia formation is essential for human life. One of the earliest events in the ciliogenesis program is the recruitment of tau-tubulin kinase 2 (TTBK2) by the centriole distal appendage component CEP164. Due to the lack of high-resolution structural information on this complex, it is unclear how it is affected in human ciliopathies such as nephronophthisis. Furthermore, it is poorly understood if binding to CEP164 influences TTBK2 activities. Here, we present a detailed biochemical, structural, and functional analysis of the CEP164-TTBK2 complex and demonstrate how it is compromised by two ciliopathic mutations in CEP164. Moreover, we also provide insights into how binding to CEP164 is coordinated with TTBK2 activities. Together, our data deepen our understanding of a crucial step in cilia formation and will inform future studies aimed at restoring CEP164 functionality in a debilitating human ciliopathy.

Links

GA19-05244S, research and development project

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

Investor: Czech Science Foundation

LM2018129, research and development project

Name: Národní infrastruktura pro biologické a medicínské zobrazování Czech-BioImaging

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

Citovat

SILVA, Ivan Rosa e, Lucia BINÓ, Christopher M. JOHNSON, Trevor J. RUTHERFORD, David NEUHAUS, Antonina ANDREEVA, Lukáš ČAJÁNEK and Mark van BREUGEL. Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies. Structure. Cambridge: Cell Press, 2022, vol. 30, No 1, p. "114-128"-"e1-e9", 25 pp. ISSN 0969-2126. Available from: https://dx.doi.org/10.1016/j.str.2021.08.007.

@article{1818485,
   author = {Silva, Ivan Rosa e and Binó, Lucia and Johnson, Christopher M. and Rutherford, Trevor J. and Neuhaus, David and Andreeva, Antonina and Čajánek, Lukáš and Breugel, Mark van},
   article_location = {Cambridge},
   article_number = {1},
   doi = {http://dx.doi.org/10.1016/j.str.2021.08.007},
   keywords = {CEP164; TTBK2; ciliaciliogenesis; ciliopathy; nephronophthisis; basal body; centriole; distal appendage; centrosome},
   language = {eng},
   issn = {0969-2126},
   journal = {Structure},
   title = {Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies},
   url = {https://www.sciencedirect.com/science/article/pii/S0969212621003026},
   volume = {30},
   year = {2022}
}

TY  - JOUR
ID  - 1818485
AU  - Silva, Ivan Rosa e - Binó, Lucia - Johnson, Christopher M. - Rutherford, Trevor J. - Neuhaus, David - Andreeva, Antonina - Čajánek, Lukáš - Breugel, Mark van
PY  - 2022
TI  - Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies
JF  - Structure
VL  - 30
IS  - 1
SP  - "114-128"-"e1-e9"
EP  - "114-128"-"e1-e9"
PB  - Cell Press
SN  - 09692126
KW  - CEP164
KW  - TTBK2
KW  - ciliaciliogenesis
KW  - ciliopathy
KW  - nephronophthisis
KW  - basal body
KW  - centriole
KW  - distal appendage
KW  - centrosome
UR  - https://www.sciencedirect.com/science/article/pii/S0969212621003026
N2  - Cilia formation is essential for human life. One of the earliest events in the ciliogenesis program is the recruitment of tau-tubulin kinase 2 (TTBK2) by the centriole distal appendage component CEP164. Due to the lack of high-resolution structural information on this complex, it is unclear how it is affected in human ciliopathies such as nephronophthisis. Furthermore, it is poorly understood if binding to CEP164 influences TTBK2 activities. Here, we present a detailed biochemical, structural, and functional analysis of the CEP164-TTBK2 complex and demonstrate how it is compromised by two ciliopathic mutations in CEP164. Moreover, we also provide insights into how binding to CEP164 is coordinated with TTBK2 activities. Together, our data deepen our understanding of a crucial step in cilia formation and will inform future studies aimed at restoring CEP164 functionality in a debilitating human ciliopathy.
ER  -

SILVA, Ivan Rosa e, Lucia BINÓ, Christopher M. JOHNSON, Trevor J. RUTHERFORD, David NEUHAUS, Antonina ANDREEVA, Lukáš ČAJÁNEK and Mark van BREUGEL. Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies. \textit{Structure}. Cambridge: Cell Press, 2022, vol.~30, No~1, p.~''114-128''-''e1-e9'', 25 pp. ISSN~0969-2126. Available from: https://dx.doi.org/10.1016/j.str.2021.08.007.

Detailed Information on Publication Record