Abstract:
:Lysosomal Ca2+ release channel TRPML1 has been suggested to regulate lysosome size by activating calmodulin (CaM). To further understand how TRPML1 and CaM regulate lysosome size, in this study, we report that inhibiting mTORC1 causes enlarged lysosomes, and the recovery of enlarged lysosomes is suppressed by inhibiting mTORC1. We also show that lysosome vacuolation induced by inhibiting TRPML1 is corrected by mTORC1 upregulation, and the facilitating effect of TRPML1 on the recovery of enlarged lysosomes is suppressed by inhibiting mTORC1. In the meantime, lysosome vacuolation induced by inhibiting CaM is corrected by mTORC1 upregulation, and mTORC1 overexpression corrects the inhibitory effect of CaM antagonist on the recovery of enlarged lysosomes. Conversely, the vacuolation induced by suppressing mTORC1 is not corrected by upregulating CaM. These data suggest that mTORC1 functions downstream of TRPML1 and CaM to regulate lysosome size. Together with our recent finding showing that TRPML1, CaM and mTORC1 form a macromolecular complex to control mTORC1 activity, we suggest that TRPML1 and CaM control lysosome fission through regulating mTORC1, identifying an mTORC1-dependent molecular mechanism for lysosomal membrane fission.
journal_name
Eur J Cell Bioljournal_title
European journal of cell biologyauthors
Yang Y,Xu M,Zhu X,Yao J,Shen B,Dong XPdoi
10.1016/j.ejcb.2019.05.001subject
Has Abstractpub_date
2019-06-01 00:00:00pages
116-123issue
2-4eissn
0171-9335issn
1618-1298pii
S0171-9335(18)30183-3journal_volume
98pub_type
杂志文章abstract::Exocytosis is mediated by high-affinity interactions between different SNARE proteins. The existence of several variants of each SNARE protein suggests that the specificity of fusion may be directed by unique combination of SNARE family members. We examined if two alternatively spliced variants of synaptosomal-associa...
journal_title:European journal of cell biology
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abstract::The concept of pilot pseudopodia is reconsidered 30 years after its inauguration (Gerisch, G., Hülser, D., Malchow, D., Wick, U., 1975. Cell communication by periodic cyclic-AMP pulses. Phil. Trans. R. Soc. Lond. B 272, 181-192). The original hypothesis stated that protruding pseudopodia serve as dynamic sensory organ...
journal_title:European journal of cell biology
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abstract::We have examined the importance of cell surface heparan sulfate proteoglycans (HSPG) in fibroblast growth factor (FGF) signaling. 3T3 cells grown under conventional conditions were much more sensitive to FGF-2 compared to FGF-1. However, cells were equally sensitive to FGF-1 and FGF-2 using conditions which reduced th...
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journal_title:European journal of cell biology
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更新日期:1981-10-01 00:00:00
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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更新日期:1992-12-01 00:00:00
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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journal_title:European journal of cell biology
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