Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases.
Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases.
复制标题
将蓇葖蛋白募集到溶酶体有助于氨基酸依赖性地激活 Rag GTP 酶。
DOI：
10.1083/jcb.201307084
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发表时间：
2013-09-30
期刊：
影响因子：
--
通讯作者：
Ferguson SM
中科院分区：
文献类型：
--
作者：
Petit CS;Roczniak-Ferguson A;Ferguson SM
Folliculin localizes to lysosomes and directly interacts with Rag GTPases, promoting mTORC1 activation, when amino acids are abundant. Birt-Hogg-Dubé syndrome, a human disease characterized by fibrofolliculomas (hair follicle tumors) as well as a strong predisposition toward the development of pneumothorax, pulmonary cysts, and renal carcinoma, arises from loss-of-function mutations in the folliculin (FLCN) gene. In this study, we show that FLCN regulates lysosome function by promoting the mTORC1-dependent phosphorylation and cytoplasmic sequestration of transcription factor EB (TFEB). Our results indicate that FLCN is specifically required for the amino acid–stimulated recruitment of mTORC1 to lysosomes by Rag GTPases. We further demonstrated that FLCN itself was selectively recruited to the surface of lysosomes after amino acid depletion and directly bound to RagA via its GTPase domain. FLCN-interacting protein 1 (FNIP1) promotes both the lysosome recruitment and Rag interactions of FLCN. These new findings define the lysosome as a site of action for FLCN and indicate a critical role for FLCN in the amino acid–dependent activation of mTOR via its direct interaction with the RagA/B GTPases.
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影响因子：
8
作者：
Hartman, T. R.;Nicolas, E.;Klein-Szanto, A.;Al-Saleem, T.;Cash, T. P.;Simon, M. C.;Henske, E. P.
通讯作者：
Henske, E. P.
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
56.9
作者：
Hillenmeyer, Maureen E.;Fung, Eula;Giaever, Guri
通讯作者：
Giaever, Guri
影响因子：
16
作者：
Kim, DH;Sarbassov, DD;Sabatini, DM
通讯作者：
Sabatini, DM
影响因子：
37.3
作者：
Hong SB;Oh H;Valera VA;Stull J;Ngo DT;Baba M;Merino MJ;Linehan WM;Schmidt LS
通讯作者：
Schmidt LS