The arf-like GTPase Arl8 mediates delivery of endocytosed macromolecules to lysosomes in Caenorhabditis elegans.
The arf-like GTPase Arl8 mediates delivery of endocytosed macromolecules to lysosomes in Caenorhabditis elegans.
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DOI：
10.1091/mbc.e09-12-1010
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发表时间：
2010-07-15
影响因子：
3.3
通讯作者：
Katada T
中科院分区：
文献类型：
--
作者：
Nakae I;Fujino T;Kobayashi T;Sasaki A;Kikko Y;Fukuyama M;Gengyo-Ando K;Mitani S;Kontani K;Katada T
晚期内涵体和溶酶体直接融合以进行内容混合，形成混合细胞器。在本研究中，我们发现秀丽隐杆线虫 ARL-8 GTP 酶主要定位于溶酶体，并参与巨噬细胞样体腔细胞中的晚期内体-溶酶体融合。包括溶酶体在内的晚期内吞细胞器是高度动态的酸性细胞器。晚期内体和溶酶体直接融合以进行内容混合，形成混合细胞器，从中重组溶酶体。目前尚不完全了解这些过程是如何监管和维护的。在这里，我们表明，秀丽隐杆线虫 ARL-8 GTP 酶主要定位于溶酶体，并参与巨噬细胞样体腔细胞中的晚期内体-溶酶体融合。 arl-8 的缺失导致晚期内体/溶酶体区室数量增加，该区室比野生型小。在arl-8突变体中，含有内吞大分子的晚期内体区室无法与富含天冬氨酸蛋白酶ASP-1的溶酶体区室融合。此外，arl-8的缺失强烈抑制了由cup-5突变引起的扩大的晚期内体-溶酶体混合细胞器的形成，cup-5是人mucolipin-1的直系同源物。这些发现表明，ARL-8 通过促进晚期内体-溶酶体融合来介导内吞大分子向溶酶体的递送。
Late endosomes and lysosomes directly fuse for content mixing to form hybrid organelles. In the present study, we show that the Caenorhabditis elegans ARL-8 GTPase is localized primarily to lysosomes and involved in late endosome-lysosome fusion in the macrophage-like coelomocytes. Late endocytic organelles including lysosomes are highly dynamic acidic organelles. Late endosomes and lysosomes directly fuse for content mixing to form hybrid organelles, from which lysosomes are reformed. It is not fully understood how these processes are regulated and maintained. Here we show that the Caenorhabditis elegans ARL-8 GTPase is localized primarily to lysosomes and involved in late endosome-lysosome fusion in the macrophage-like coelomocytes. Loss of arl-8 results in an increase in the number of late endosomal/lysosomal compartments, which are smaller than wild type. In arl-8 mutants, late endosomal compartments containing endocytosed macromolecules fail to fuse with lysosomal compartments enriched in the aspartic protease ASP-1. Furthermore, loss of arl-8 strongly suppresses formation of enlarged late endosome-lysosome hybrid organelles caused by mutations of cup-5, which is the orthologue of human mucolipin-1. These findings suggest that ARL-8 mediates delivery of endocytosed macromolecules to lysosomes by facilitating late endosome-lysosome fusion.
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DOI：
10.1006/bbrc.2000.2260
发表时间：
2000-03-05
影响因子：
3.1
作者：
Gengyo-Ando, K;Mitani, S
通讯作者：
Mitani, S
影响因子：
3.3
作者：
Hermann, GJ;Schroeder, LK;Priess, JR
通讯作者：
Priess, JR
影响因子：
4.8
作者：
Li, YW;Kelly, WG;Kahn, RA
通讯作者：
Kahn, RA
影响因子：
12.3
作者：
通讯作者：
--
影响因子：
4
作者：
Hofmann, I;Munro, S
通讯作者：
Munro, S