A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission.
A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission.
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一类新的ER膜蛋白调节与ER相关的内体裂变。
DOI：
10.1016/j.cell.2018.08.030
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发表时间：
2018-09-20
期刊：
影响因子：
64.5
通讯作者：
Voeltz GK
中科院分区：
文献类型：
--
作者：
Hoyer MJ;Chitwood PJ;Ebmeier CC;Striepen JF;Qi RZ;Old WM;Voeltz GK
ER膜接触位点（MCS）标记内体经历分裂以进行货物分选的位置。为了定义ER在这种独特的MCS中的作用，我们将混杂的生物素连接酶靶向核内体芽上的货物分选结构域。该策略鉴定了ER膜蛋白TMCC 1，其为保守蛋白家族的成员。TMCC 1集中在ER-内体MCS，其在空间和时间上与内体分裂相关。当TMCC 1耗尽时，内体形态是正常的，芽仍然形成，但ER相关的芽分裂和随后的货物分选到高尔基体受损。我们发现，内质网相关的肌动蛋白依赖的货物分选结构域的裂变所需的内体定位的肌动蛋白调节Coronin 1C。Coronin 1C独立于TMCC 1被募集到核内体芽，而TMCC 1/ER募集需要Coronin 1C。TMCC 1和Coronin 1C之间的这种联系表明，TMCC 1依赖性ER募集的时间是在货物被适当地隔离到萌芽中之后被严格调节的。内体分裂的时间和位置由TMCC 1介导的ER募集到ER-膜接触来严格调节，以确保只有货物被适当地隔离才发生出芽。
ER membrane contact sites (MCSs) mark positions where endosomes undergo fission for cargo sorting. To define the role of ER at this unique MCS, we targeted a promiscuous biotin ligase to cargo sorting domains on endosome buds. This strategy identified the ER membrane protein TMCC1, a member of a conserved protein family. TMCC1 concentrates at the ER-endosome MCSs that are spatially and temporally linked to endosome fission. When TMCC1 is depleted, endosome morphology is normal, buds still form, but ER-associated bud fission and subsequent cargo sorting to the Golgi are impaired. We find that the endosome-localized actin regulator Coronin1C is required for ER-associated fission of actin-dependent cargo sorting domains. Coronin1C is recruited to endosome buds independently of TMCC1, while TMCC1/ER recruitment requires Coronin1C. This link between TMCC1 and Coronin1C suggests the timing of TMCC1-dependent ER recruitment is tightly regulated to occur after cargo has been properly sequestered into the bud. The timing and location of endosome fission is tightly regulated by TMCC1-mediated ER recruitment to ER-membrane contact to ensure that budding happens only cargo has been properly sequestered.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.1083/jcb.200911024
发表时间：
2010-08-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Friedman JR;Webster BM;Mastronarde DN;Verhey KJ;Voeltz GK
通讯作者：
Voeltz GK
DOI：
10.1083/jcb.201609033
发表时间：
2017-05-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Allison R;Edgar JR;Pearson G;Rizo T;Newton T;Günther S;Berner F;Hague J;Connell JW;Winkler J;Lippincott-Schwartz J;Beetz C;Winner B;Reid E
通讯作者：
Reid E
DOI：
10.1042/bj20120209
发表时间：
2012-05-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Chan KT;Roadcap DW;Holoweckyj N;Bear JE
通讯作者：
Bear JE
影响因子：
7.2
作者：
Gautreau, Alexis;Oguievetskaia, Ksenia;Ungermann, Christian
通讯作者：
Ungermann, Christian