BLOC-1 and BLOC-3 regulate VAMP7 cycling to and from melanosomes via distinct tubular transport carriers.
BLOC-1 and BLOC-3 regulate VAMP7 cycling to and from melanosomes via distinct tubular transport carriers.
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DOI：
10.1083/jcb.201605090
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发表时间：
2016-08-01
期刊：
影响因子：
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通讯作者：
Marks MS
中科院分区：
文献类型：
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作者：
Dennis MK;Delevoye C;Acosta-Ruiz A;Hurbain I;Romao M;Hesketh GG;Goff PS;Sviderskaya EV;Bennett DC;Luzio JP;Galli T;Owen DJ;Raposo G;Marks MS
Dennis等人分析了黑素细胞中黑素体生物发生期间v-SNARE VAMP 7的循环。VAMP 7被靶向到在单独的管状载体中的成熟的黑素体并从其回收，所述管状载体的形成需要不同的BLOC，每个BLOC在Hermansky-Pudlak综合征的变体中有缺陷。内膜细胞器成熟需要通过与膜运输中间体融合和融合因子再循环到其起源位点的货物递送。黑素体和其他溶酶体相关的细胞器从早期的内体获得货物，但涉及的融合机制及其再循环途径尚不清楚。在这里，我们表明，v-SNARE VAMP 7介导的黑素体与管状运输载体，也携带货物蛋白TYRP 1和需要BLOC-1为他们的形成融合。使用活细胞成像，我们确定了VAMP 7从黑素体回收的途径，采用不同的管状载体。再循环载体还含有VAMP 7结合支架蛋白VARP和组织限制性Rab GT3 RAB 38。再循环载体的形成依赖于RAB 38交换因子BLOC-3。我们的数据表明，VAMP 7介导BLOC-1依赖性转运载体与黑素体的融合，阐明黑素体的SNARE再循环是BLOC-3依赖性的关键步骤，并可能解释Hermansky-Pudlak综合征变体中与BLOC-1和BLOC-3缺陷相关的不同色素减退表型。
Dennis et al. analyze cycling of the v-SNARE VAMP7 during melanosome biogenesis in melanocytes. VAMP7 is targeted to and retrieved from maturing melanosomes in separate tubular carriers whose formation requires distinct BLOCs, each defective in variants of Hermansky–Pudlak syndrome. Endomembrane organelle maturation requires cargo delivery via fusion with membrane transport intermediates and recycling of fusion factors to their sites of origin. Melanosomes and other lysosome-related organelles obtain cargoes from early endosomes, but the fusion machinery involved and its recycling pathway are unknown. Here, we show that the v-SNARE VAMP7 mediates fusion of melanosomes with tubular transport carriers that also carry the cargo protein TYRP1 and that require BLOC-1 for their formation. Using live-cell imaging, we identify a pathway for VAMP7 recycling from melanosomes that employs distinct tubular carriers. The recycling carriers also harbor the VAMP7-binding scaffold protein VARP and the tissue-restricted Rab GTPase RAB38. Recycling carrier formation is dependent on the RAB38 exchange factor BLOC-3. Our data suggest that VAMP7 mediates fusion of BLOC-1–dependent transport carriers with melanosomes, illuminate SNARE recycling from melanosomes as a critical BLOC-3–dependent step, and likely explain the distinct hypopigmentation phenotypes associated with BLOC-1 and BLOC-3 deficiency in Hermansky–Pudlak syndrome variants.