Infection-driven activation of transglutaminase 2 boosts glucose uptake and hexosamine biosynthesis in epithelial cells.
Animals
Biological Transport
Chlamydia Infections
/ metabolism
Chlamydia trachomatis
/ physiology
Epithelial Cells
/ metabolism
Fibroblasts
Fructosephosphates
/ metabolism
GTP-Binding Proteins
/ genetics
Gene Expression Regulation, Enzymologic
Glucosamine
/ metabolism
Glucose
/ metabolism
HeLa Cells
Hexosamines
/ biosynthesis
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Glutamine gamma Glutamyltransferase 2
Transglutaminases
/ genetics
Chlamydia
GFPT
O-GlcNAcylation
hexosamine biosynthesis
transglutaminase 2
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 04 2020
15 04 2020
Historique:
received:
03
04
2019
revised:
21
01
2020
accepted:
31
01
2020
pubmed:
7
3
2020
medline:
15
12
2020
entrez:
6
3
2020
Statut:
ppublish
Résumé
Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme with transamidating activity. We report here that both expression and activity of TG2 are enhanced in mammalian epithelial cells infected with the obligate intracellular bacteria Chlamydia trachomatis. Genetic or pharmacological inhibition of TG2 impairs bacterial development. We show that TG2 increases glucose import by up-regulating the transcription of the glucose transporter genes GLUT-1 and GLUT-3. Furthermore, TG2 activation drives one specific glucose-dependent pathway in the host, i.e., hexosamine biosynthesis. Mechanistically, we identify the glucosamine:fructose-6-phosphate amidotransferase (GFPT) among the substrates of TG2. GFPT modification by TG2 increases its enzymatic activity, resulting in higher levels of UDP-N-acetylglucosamine biosynthesis and protein O-GlcNAcylation. The correlation between TG2 transamidating activity and O-GlcNAcylation is disrupted in infected cells because host hexosamine biosynthesis is being exploited by the bacteria, in particular to assist their division. In conclusion, our work establishes TG2 as a key player in controlling glucose-derived metabolic pathways in mammalian cells, themselves hijacked by C. trachomatis to sustain their own metabolic needs.
Identifiants
pubmed: 32134139
doi: 10.15252/embj.2019102166
pmc: PMC7156965
doi:
Substances chimiques
Fructosephosphates
0
Hexosamines
0
fructose-6-phosphate
6814-87-5
Protein Glutamine gamma Glutamyltransferase 2
EC 2.3.2.13
Transglutaminases
EC 2.3.2.13
GTP-Binding Proteins
EC 3.6.1.-
Glucose
IY9XDZ35W2
Glucosamine
N08U5BOQ1K
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e102166Subventions
Organisme : Centre National de la Recherche Scientifique
Pays : International
Organisme : ERC
ID : 282046
Pays : International
Organisme : Institut Pasteur
Pays : International
Organisme : Cancéropole Ile-de-France
Pays : International
Organisme : GEFLUC
Pays : International
Organisme : European Research Council
ID : 282046
Pays : International
Organisme : Ministère de l'Education Nationale, de la Recherche et de la Technologie
Pays : International
Informations de copyright
© 2020 The Authors.
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