The TOG5 domain of CKAP5 is required to interact with F-actin and promote microtubule advancement in neurons

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00602186" target="_blank" >RIV/86652036:_____/24:00602186 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/24:10489383

Výsledek na webu

<a href="https://www.molbiolcell.org/doi/abs/10.1091/mbc.E24-05-0202" target="_blank" >https://www.molbiolcell.org/doi/abs/10.1091/mbc.E24-05-0202</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1091/mbc.E24-05-0202" target="_blank" >10.1091/mbc.E24-05-0202</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The TOG5 domain of CKAP5 is required to interact with F-actin and promote microtubule advancement in neurons

Popis výsledku v původním jazyce

Microtubule (MT) and F-actin cytoskeletal cross-talk and organization are important aspects of axon guidance mechanisms, but how associated proteins facilitate this function remains largely unknown. While the MT-associated protein, CKAP5 (XMAP215/chTOG), has been best characterized as a MT polymerase, we have recently highlighted a novel role for CKAP5 in facilitating interactions between MT and F-actin in vitro and in embryonic Xenopus laevis neuronal growth cones. However, the mechanism by which it does so is unclear. Here, using in vitro reconstitution assays coupled with total internal reflection fluorescence microscopy, we report that the TOG5 domain of CKAP5 is necessary for its ability to bind to and bundle actin filaments, as well as to cross-link MTs and F-actin in vitro. Additionally, we show that this novel MT/F-actin cross-linking function of CKAP5 is possible even in MT polymerase-incompetent mutants of CKAP5 in vivo. Indeed, CKAP5 requires both MT and F-actin binding, but not MT polymerization, to promote MT-F-actin alignment in growth cones and axon outgrowth. Taken together, our findings provide mechanistic insights into how MT populations penetrate the growth cone periphery through CKAP5facilitated interaction with F-actin during axon outgrowth and guidance.

Název v anglickém jazyce

The TOG5 domain of CKAP5 is required to interact with F-actin and promote microtubule advancement in neurons

Popis výsledku anglicky

Microtubule (MT) and F-actin cytoskeletal cross-talk and organization are important aspects of axon guidance mechanisms, but how associated proteins facilitate this function remains largely unknown. While the MT-associated protein, CKAP5 (XMAP215/chTOG), has been best characterized as a MT polymerase, we have recently highlighted a novel role for CKAP5 in facilitating interactions between MT and F-actin in vitro and in embryonic Xenopus laevis neuronal growth cones. However, the mechanism by which it does so is unclear. Here, using in vitro reconstitution assays coupled with total internal reflection fluorescence microscopy, we report that the TOG5 domain of CKAP5 is necessary for its ability to bind to and bundle actin filaments, as well as to cross-link MTs and F-actin in vitro. Additionally, we show that this novel MT/F-actin cross-linking function of CKAP5 is possible even in MT polymerase-incompetent mutants of CKAP5 in vivo. Indeed, CKAP5 requires both MT and F-actin binding, but not MT polymerization, to promote MT-F-actin alignment in growth cones and axon outgrowth. Taken together, our findings provide mechanistic insights into how MT populations penetrate the growth cone periphery through CKAP5facilitated interaction with F-actin during axon outgrowth and guidance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Molecular Biology of the Cell

ISSN

1059-1524

e-ISSN

1939-4586

Svazek periodika

35

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

br24

Kód UT WoS článku

001363454400003

EID výsledku v databázi Scopus

2-s2.0-85210453581