Eukaryote-Wide Distribution of a Family of Longin Domain-Containing GAP Complexes for Small GTPases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F25%3A00637874" target="_blank" >RIV/60077344:_____/25:00637874 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1111/tra.70016" target="_blank" >https://doi.org/10.1111/tra.70016</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/tra.70016" target="_blank" >10.1111/tra.70016</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Eukaryote-Wide Distribution of a Family of Longin Domain-Containing GAP Complexes for Small GTPases

Popis výsledku v původním jazyce

Arf and Rab family small GTPases and their regulators, GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), play a central role in membrane trafficking. In this study, we focused on a recently reported GAP for Arf (and potentially Rab) proteins, the CSW complex, a part of a small family of longin domain-containing proteins that form complexes with GAP activity. This family also includes folliculin and GATOR1, which are GAPs for the Rag/Gtr GTPases. All three complexes are associated with lysosomes and play a role in nutrient signaling, the latter two being directly involved in the mTOR pathway. The role of CSW is not clear, but in addition to having GAP activity on Arf proteins in vitro, its mutation causes severe neurodegenerative diseases. Here we update the reported pan-eukaryotic presence of folliculin and GATOR1, and demonstrate that CSW is also found throughout eukaryotes, though with sporadic distribution. We identify highly conserved motifs in all CSW subunits, some shared with the catalytic subunits of folliculin and GATOR1, that provide new potential avenues for experimental exploration. Remarkably, one such conserved sequence, the GP motif, is also found in structurally related longin proteins present in the archaeal ancestor of eukaryotes.

Název v anglickém jazyce

Eukaryote-Wide Distribution of a Family of Longin Domain-Containing GAP Complexes for Small GTPases

Popis výsledku anglicky

Arf and Rab family small GTPases and their regulators, GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), play a central role in membrane trafficking. In this study, we focused on a recently reported GAP for Arf (and potentially Rab) proteins, the CSW complex, a part of a small family of longin domain-containing proteins that form complexes with GAP activity. This family also includes folliculin and GATOR1, which are GAPs for the Rag/Gtr GTPases. All three complexes are associated with lysosomes and play a role in nutrient signaling, the latter two being directly involved in the mTOR pathway. The role of CSW is not clear, but in addition to having GAP activity on Arf proteins in vitro, its mutation causes severe neurodegenerative diseases. Here we update the reported pan-eukaryotic presence of folliculin and GATOR1, and demonstrate that CSW is also found throughout eukaryotes, though with sporadic distribution. We identify highly conserved motifs in all CSW subunits, some shared with the catalytic subunits of folliculin and GATOR1, that provide new potential avenues for experimental exploration. Remarkably, one such conserved sequence, the GP motif, is also found in structurally related longin proteins present in the archaeal ancestor of eukaryotes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Traffic

ISSN

1398-9219

e-ISSN

1600-0854

Svazek periodika

26

Číslo periodika v rámci svazku

7-9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

e70016

Kód UT WoS článku

001536285600001

EID výsledku v databázi Scopus

2-s2.0-105011851823