SARS-CoV-2 Spike Protein Downregulates Cell Surface α7nAChR through a Helical Motif in the Spike Neck.
ACS Chem Neurosci
; 14(4): 689-698, 2023 02 15.
Artigo
em Inglês
| MEDLINE | ID: covidwho-2236297
ABSTRACT
A deficiency of the functional α7 nicotinic acetylcholine receptor (α7nAChR) impairs neuronal and immune systems. The SARS-CoV-2 spike protein (S12) facilitates virus cell entry during COVID-19 infection and can also independently disrupt cellular functions. Here, we found that S12 expression significantly downregulated surface expression of α7nAChR in mammalian cells. A helical segment of S12 (L1145-L1152) in the spike neck was identified to be responsible for the downregulation of α7nAChR, as the mutant S12AAA (L1145A-F1148A-L1152A) had minimal effects on surface α7nAChR expression. This S12 segment is homologous to the α7nAChR intracellular helical motif known for binding chaperone proteins RIC3 and Bcl-2 to promote α7nAChR surface expression. Competition from S12 for binding these proteins likely underlies suppression of surface α7nAChR. Considering the critical roles of α7nAChR in cellular functions, these findings provide a new perspective for improving mRNA vaccines and developing treatment options for certain symptoms related to long COVID.
Palavras-chave
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Receptor Nicotínico de Acetilcolina alfa7
/
COVID-19
Tipo de estudo:
Estudo prognóstico
Tópicos:
Covid persistente
/
Vacinas
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
ACS Chem Neurosci
Ano de publicação:
2023
Tipo de documento:
Artigo
País de afiliação:
Acschemneuro.2c00610
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