Longin domain GAP complexes in nutrient signalling, membrane traffic and neurodegeneration.
FEBS Lett
; 597(6): 750-761, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36367440
ABSTRACT
Small GTPases act as molecular switches and control numerous cellular processes by their binding and hydrolysis of guanosine triphosphate (GTP). The activity of small GTPases is coordinated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Recent structural and functional studies have characterized a subset of GAPs whose catalytic units consist of longin domains. Longin domain containing GAPs regulate small GTPases that facilitate nutrient signalling, autophagy, vesicular trafficking and lysosome homeostasis. All known examples in this GAP family function as part of larger multiprotein complexes. The three characterized mammalian protein complexes in this class are FLCNFNIP, GATOR1 and C9orf72SMCR8. Each complex carries out a unique cellular function by regulating distinct small GTPases. In this article, we explore the roles of longin domain GAPs in nutrient sensing, membrane dynamic, vesicular trafficking and disease. Through a structural lens, we examine the mechanism of each longin domain GAP and highlight potential therapeutic applications.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Proteínas Monoméricas de Ligação ao GTP
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article