Normal lytic granule secretion by cytotoxic T lymphocytes deficient in BLOC-1, -2 and -3 and myosins Va, VIIa and XV
Normal lytic granule secretion by cytotoxic T lymphocytes deficient in BLOC-1, -2 and -3 and myosins Va, VIIa and XV
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DOI：
10.1111/j.1600-0854.2005.00264.x
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发表时间：
2005-03-01
期刊：
影响因子：
4.5
通讯作者：
Griffiths, GM
中科院分区：
文献类型：
--
作者：
Bossi, G;Booth, S;Griffiths, GM
黑素细胞和免疫系统细胞具有不寻常的分泌机制，利用溶酶体作为受调节的分泌细胞器。最近，已经鉴定出这些“分泌性溶酶体”进行胞吐作用所需的许多蛋白质。这些包括 Rab27a、Lyst、Rab 香叶基香叶基转移酶和接头蛋白复合物 AP-3。缺乏任何这些蛋白质的患者的特征是白化病和免疫缺陷的罕见组合，揭示了这些蛋白质在黑素细胞和免疫细胞分泌中的作用。为了探究白化病和免疫缺陷之间的联系有多远，我们检查了两名 BLOC-3 缺陷患者和七种不同的 Hermansky-Pudlak 综合征小鼠模型的细胞毒性 T 淋巴细胞 (CTL) 分泌，所有这些小鼠模型都表现出色素沉着和血小板功能缺陷。我们发现HPS患者和缺乏BLOC-3的苍耳小鼠、缺乏BLOC-1的苍白、静音和沙色小鼠、缺乏BLOC-2的红宝石眼小鼠和缺乏Vps33a的浅黄色小鼠的CTL功能正常。同样，非常规肌球蛋白 Va、VIIa 和 XV 在某些细胞类型中可充当 Rab27a 的效应子，但在 CTL 中并不需要。这些结果揭示了 CTL 和黑素细胞中溶酶体相关细胞器的生物发生和/或分泌所需的蛋白质机制的差异。
Melanocytes and cells of the immune system share an unusual secretory mechanism which uses the lysosome as a regulated secretory organelle. Recently, a number of the proteins required for these 'secretory lysosomes' to undergo exocytosis have been identified. These include Rab27a, Lyst, Rab geranyl geranyl transferase and the adapter protein complex AP-3. Patients lacking any of these proteins are characterized by the rare combination of albinism and immunodeficiency, revealing roles for these proteins in both melanocyte and immune cell secretion. In order to ask how far the link between albinism and immunodeficiency extends we have examined cytotoxic T-lymphocyte (CTL) secretion from two BLOC-3-deficient patients and seven different mouse models of Hermansky-Pudlak syndrome, all of which display defects in pigmentation and platelet function. We find that CTL function is normal in HPS patients and pale-ear mice deficient in BLOC-3, pallid, muted and sandy mice deficient in BLOC-1, ruby-eye mice deficient in BLOC-2 and buff mice deficient in Vps33a. Similarly, the unconventional myosins, Va, VIIa and XV, which can act as effectors for Rab27a in some cell types, are not required in CTL. These results reveal differences in the protein machinery required for biogenesis and/or secretion of lysosome-related organelles in CTL and melanocytes.