Rab9-dependent retrograde transport and endosomal sorting of the endopeptidase furin
Rab9-dependent retrograde transport and endosomal sorting of the endopeptidase furin
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DOI：
10.1242/jcs.083782
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发表时间：
2011-07-15
影响因子：
4
通讯作者：
Gleeson, Paul A.
中科院分区：
文献类型：
--
作者：
Chia, Pei Zhi Cheryl;Gasnereau, Isabelle;Gleeson, Paul A.
内肽酶弗林蛋白酶和反式高尔基体网络蛋白TGN 38是在TGN和质膜之间再循环的膜蛋白。TGN 38通过逆转录依赖性途径从早期内体转运至TGN，而弗林蛋白酶的细胞内转运定义不清。这里我们已经确定了弗林的行程和运输要求。使用内化分析，我们表明，弗林蛋白酶过境的早期和晚期内涵体途中的TGN。晚期内体至TGN通路的组分GTGFRab 9和TGN golgin GCC 185是有效的TGN回收弗林蛋白酶所必需的。相比之下，TGN 38的运输独立于Rab 9和GCC 185。为了鉴定早期内体至TGN途径的分选信号，研究了弗林蛋白酶-TGN 38嵌合体的运输。弗林蛋白酶从Rab 9依赖性晚期内体-TGN途径转向逆转录依赖性早期内体-TGN途径需要TGN 38的跨膜结构域和胞质尾区。我们目前的证据表明，跨膜结构域的长度是一个内体分选的影响因素。总之，这些数据表明，弗林蛋白酶使用Rab 9依赖性途径从晚期内体和逆行运输直接从早期内体是依赖于跨膜结构域和胞质尾。
The endopeptidase furin and the trans-Golgi network protein TGN38 are membrane proteins that recycle between the TGN and plasma membrane. TGN38 is transported by a retromer-dependent pathway from early endosomes to the TGN, whereas the intracellular transport of furin is poorly defined. Here we have identified the itinerary and transport requirements of furin. Using internalisation assays, we show that furin transits the early and late endosomes en route to the TGN. The GTPase Rab9 and the TGN golgin GCC185, components of the late endosome-to-TGN pathway, were required for efficient TGN retrieval of furin. By contrast, TGN38 trafficking was independent of Rab9 and GCC185. To identify the sorting signals for the early endosome-to-TGN pathway, the trafficking of furin-TGN38 chimeras was investigated. The diversion of furin from the Rab9-dependent late-endosome-to-TGN pathway to the retromer-dependent early-endosome-to-TGN pathway required both the transmembrane domain and cytoplasmic tail of TGN38. We present evidence to suggest that the length of the transmembrane domain is a contributing factor in endosomal sorting. Overall, these data show that furin uses the Rab9-dependent pathway from late endosomes and that retrograde transport directly from early endosomes is dependent on both the transmembrane domain and the cytoplasmic tail.