The new target of Rapamycin: lysosomal calcium channel TRPML1 / 生理学报
Acta Physiologica Sinica
;
(6): 137-142, 2021.
Artigo
em Chinês
| WPRIM
| ID: wpr-878243
ABSTRACT
Rapamycin (Rap) is an immunosuppressant, which is mainly used in the anti-rejection of organ transplantation. Meanwhile, it also shows great potential in the fields of anticancer, neuroprotection and anti-aging. Rap can inhibit the activity of mammalian target of Rap (mTOR). It activates the transcription factor EB (TFEB) to up-regulate lysosomal function and eliminates the inhibitory effect of mTOR on ULK1 (unc-51 like autophagy activating kinase 1) to promote autophagy. Recent research showed that Rap can directly activate the lysosomal cation channel TRPML1 in an mTOR-independent manner. TRPML1 activation releases lysosomal calcium. Calcineurin functions as the sensor of the lysosomal calcium signal and activates TFEB, thus promoting lysosome function and autophagy. This finding has greatly broadened and deepened our understanding of the pharmacological roles of Rap. In this review, we briefly introduce the canonical Rap-mTOR-ULK1/TFEB signaling pathway, and then discuss the discovery of TRPML1 as a new target of Rap and the pharmacological potential of this novel Rap-TRPML1-Calcineurin-TFEB pathway.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Autofagia
/
Canais de Cálcio
/
Transdução de Sinais
/
Cálcio
/
Sirolimo
/
Lisossomos
Idioma:
Chinês
Revista:
Acta Physiologica Sinica
Ano de publicação:
2021
Tipo de documento:
Artigo
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