RESUMO
The lysosomal membrane protein TMEM106B functions as a proviral factor in SARS-CoV-2 infection, though it was not known how. In this issue of Cell, Baggen et al. demonstrate that TMEM106B serves as an ACE2-independent receptor for SARS-CoV-2 entry by promoting the fusion of the viral membrane with the lysosomal membrane.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Internalização do Vírus , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas do Tecido NervosoRESUMO
TMEM106B, encoding a lysosome membrane protein, has been recently associated with brain aging, hypomyelinating leukodystrophy and multiple neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). During the past decade, considerable progress has been made towards our understanding of the cellular and physiological functions of TMEM106B. TMEM106B regulates many aspects of lysosomal function, including lysosomal pH, lysosome movement, and lysosome exocytosis. Both an increase and decrease in TMEM106B levels result in lysosomal abnormalities. In mouse models, TMEM106B deficiency leads to lysosome trafficking and myelination defects and FTLD related pathology. In humans, alterations in TMEM106B levels or function are intimately linked to neuronal proportions, brain aging, and brain disorders. Further elucidation of the physiological function of TMEM106B and changes in TMEM106B under pathological conditions will facilitate therapeutic development to treat brain disorders associated with TMEM106B.