Functions and mechanisms of the GPCR adaptor protein Norbin.
GPCR
NCDN
Norbin
P-Rex1
Rac
neurochondrin
Journal
Biochemical Society transactions
ISSN: 1470-8752
Titre abrégé: Biochem Soc Trans
Pays: England
ID NLM: 7506897
Informations de publication
Date de publication:
31 08 2023
31 08 2023
Historique:
received:
08
02
2023
revised:
27
06
2023
accepted:
07
07
2023
medline:
31
8
2023
pubmed:
28
7
2023
entrez:
28
7
2023
Statut:
ppublish
Résumé
Norbin (Neurochondrin, NCDN) is a highly conserved 79 kDa adaptor protein that was first identified more than a quarter of a century ago as a gene up-regulated in rat hippocampus upon induction of long-term potentiation. Most research has focussed on the role of Norbin in the nervous system, where the protein is highly expressed. Norbin regulates neuronal morphology and synaptic plasticity, and is essential for normal brain development and homeostasis. Dysregulation of Norbin is linked to a variety of neurological conditions. Recently, Norbin was shown to be expressed in myeloid cells as well as neurons. Myeloid-cell specific deletion revealed an important role of Norbin as a suppressor of neutrophil-derived innate immunity. Norbin limits the ability of neutrophils to clear bacterial infections by curbing the responsiveness of these cells to inflammatory and infectious stimuli. Mechanistically, Norbin regulates cell responses through binding to its interactors, in particular to a wide range of G protein-coupled receptors (GPCRs). Norbin association with GPCRs controls GPCR trafficking and signalling. Other important Norbin interactors are the Rac guanine-nucleotide exchange factor P-Rex1 and protein kinase A. Downstream signalling pathways regulated by Norbin include ERK, Ca2+ and the small GTPase Rac. Here, we review the current understanding of Norbin structure, expression and its roles in health and disease. We also explore Norbin signalling through its interactors, with a particular focus on GPCR trafficking and signalling. Finally, we discuss avenues that could be pursued in the future to increase our understanding of Norbin biology.
Identifiants
pubmed: 37503670
pii: 233327
doi: 10.1042/BST20221349
pmc: PMC10586782
doi:
Substances chimiques
norbin
0
Neuropeptides
0
Receptors, G-Protein-Coupled
0
Guanine Nucleotide Exchange Factors
0
Adaptor Proteins, Signal Transducing
0
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1545-1558Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P013384/1
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Informations de copyright
© 2023 The Author(s).
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