Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F19%3A00521183" target="_blank" >RIV/86652036:_____/19:00521183 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41556-019-0374-6" target="_blank" >https://www.nature.com/articles/s41556-019-0374-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41556-019-0374-6" target="_blank" >10.1038/s41556-019-0374-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes

Popis výsledku v původním jazyce

Tau is an intrinsically disordered protein, which diffuses on microtubules(1). In neurodegenerative diseases, collectively termed tauopathies, malfunction of tau and its detachment from axonal microtubules are correlated with axonal degeneration(2). Tau can protect microtubules from microtubuledegrading enzymes such as katanin(3). However, how tau carries out this regulatory function is still unclear. Here, using in vitro reconstitution, we show that tau molecules on microtubules cooperatively form cohesive islands that are kinetically distinct from tau molecules that individually diffuse on microtubules. Dependent on the tau concentration in solution, the islands reversibly grow or shrink by addition or release of tau molecules at their boundaries. Shielding microtubules from kinesin-1 motors and katanin, the islands exhibit regulatory qualities distinct from a comparably dense layer of diffusible tau. Superprocessive kinesin-8 motors penetrate the islands and cause their disassembly. Our results reveal a microtubule-dependent phase of tau that constitutes an adaptable protective layer on the microtubule surface. We anticipate that other intrinsically disordered axonal proteins display a similar cooperative behaviour and potentially compete with tau in regulating access to the microtubule surface.

Název v anglickém jazyce

Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes

Popis výsledku anglicky

Tau is an intrinsically disordered protein, which diffuses on microtubules(1). In neurodegenerative diseases, collectively termed tauopathies, malfunction of tau and its detachment from axonal microtubules are correlated with axonal degeneration(2). Tau can protect microtubules from microtubuledegrading enzymes such as katanin(3). However, how tau carries out this regulatory function is still unclear. Here, using in vitro reconstitution, we show that tau molecules on microtubules cooperatively form cohesive islands that are kinetically distinct from tau molecules that individually diffuse on microtubules. Dependent on the tau concentration in solution, the islands reversibly grow or shrink by addition or release of tau molecules at their boundaries. Shielding microtubules from kinesin-1 motors and katanin, the islands exhibit regulatory qualities distinct from a comparably dense layer of diffusible tau. Superprocessive kinesin-8 motors penetrate the islands and cause their disassembly. Our results reveal a microtubule-dependent phase of tau that constitutes an adaptable protective layer on the microtubule surface. We anticipate that other intrinsically disordered axonal proteins display a similar cooperative behaviour and potentially compete with tau in regulating access to the microtubule surface.

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

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Nature Cell Biology

ISSN

1465-7392

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

1086-1092

Kód UT WoS článku

000484363700007

EID výsledku v databázi Scopus

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