DENN domain-containing protein FAM45A regulates the homeostasis of late/multivesicular endosomes.
DENN domain-containing protein FAM45A regulates the homeostasis of late/multivesicular endosomes.
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含有 DENN 结构域的蛋白 FAM45A 调节晚期/多囊泡内体的稳态。
DOI：
10.1016/j.bbamcr.2019.02.006
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发表时间：
2019-02
影响因子：
5.1
通讯作者：
Zhang Yanling
中科院分区：
文献类型：
--
作者：
Zhang Jianjian;Zhang Kangning;Qi Lijuan;Hu Qiuming;Shen Zhen;Liu Bowen;Deng Jiaxin;Zhang Changsong;Zhang Yanling
DENN（差异表达的异常细胞和肿瘤）结构域蛋白是一个鸟嘌呤核苷酸交换因子（GEFs）家族，用于rabb小gtp酶，并协调过多的细胞膜内运输事件。FAM45A是一种非经典DENN结构域蛋白，其功能尚不清楚。在这项研究中，我们表征了FAM45A的细胞作用。我们发现FAM45A主要定位于晚泡/多泡核内体。FAM45A的缺失导致核内体聚集在核周区域。在FAM45A基因敲低的细胞中，EGF受体的内吞作用受到损害，这是由于早期到晚期内体转化的延迟。此外，FAM45A敲除细胞中所选择的外泌体亚群的分泌也被减弱。与这些结果一致的是，Rab27a和Rab27b这两种参与内核体运动和外核体生物发生的Rabs被发现作用于FAM45A途径的下游。FAM45A与Rab27a/b共定位，并以核苷酸依赖的方式与它们形成复合物。综上所述，FAM45A可能通过激活Rab27a/b等Rab蛋白，在后期内吞噬途径的稳态中定义了一个新的调控步骤，包括内体定位、成熟和分泌。
DENN (differentiallyexpressed innormal cells andneoplasia) domain-containing proteins are a family of guanine nucleotide exchange factors (GEFs) for Rab small GTPases and coordinate a plethora of intracellular membrane trafficking events. FAM45A is a non-classical DENN domain protein, whose function was unknown. In this study, we characterized cellular roles of FAM45A. We found that FAM45A localized mainly in late/multivesicular endosomes. Depletion of FAM45A resulted in clustering of endosomes to the perinuclear region. The endocytosis of EGF receptor was impaired in FAM45A knockdown cells due to a delay in the early-to-late endosome transition. Furthermore, the secretion of selected exosome subpopulations was also attenuated in FAM45A knockdown cells. Consistent with these results, Rab27a and Rab27b, two Rabs involved in endosome motility and exosome biogenesis, were found to act downstream of FAM45A pathway. FAM45A colocalized with Rab27a/b and formed complex with them in a nucleotide-dependent manner. Taken together, FAM45A defines a novel regulatory step in the homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion, possibly through activating Rab proteins such as Rab27a/b.
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影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
Pfam：氏族、网络工具和服务。
影响因子：
14.9
作者：
Finn, Robert D.;Mistry, Jaina;Schuster-Bockler, Benjamin;Griffiths-Jones, Sam;Hollich, Volker;Lassmann, Timo;Moxon, Simon;Marshall, Mhairi;Khanna, Ajay;Durbin, Richard;Eddy, Sean R.;Sonnhammer, Erik L. L.;Bateman, Alex
通讯作者：
Bateman, Alex
DOI：
10.1083/jcb.200811005
发表时间：
2009-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rocha N;Kuijl C;van der Kant R;Janssen L;Houben D;Janssen H;Zwart W;Neefjes J
通讯作者：
Neefjes J
影响因子：
7.1
作者：
Sullivan PM;Zhou X;Robins AM;Paushter DH;Kim D;Smolka MB;Hu F
通讯作者：
Hu F