The AP3 adaptor is involved in the transport of membrane proteins to acidocalcisomes of Leishmania
The AP3 adaptor is involved in the transport of membrane proteins to acidocalcisomes of Leishmania
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DOI：
10.1242/jcs.022574
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发表时间：
2008-03-01
影响因子：
4
通讯作者：
Mottram, Jeremy C.
中科院分区：
文献类型：
--
作者：
Besteiro, Sebastien;Tonn, Daniela;Mottram, Jeremy C.
溶酶体功能对寄生原虫硕大利什曼原虫的分化和感染性至关重要。为了研究溶酶体的生物发生，一个L。产生接头蛋白3（AP 3 δ）复合物δ亚基缺陷的主要突变体。结构和蛋白水解能力的溶酶体室显然是不受影响的AP 3缺陷突变体，但是，缺陷被确定在其acidocalcisomes。这些是富含钙和磷的酸性细胞器，从细菌到真核生物都有，其功能仍然是个谜。L.主要的突变体缺乏膜结合质子泵（特别是V-H+-PPase），比正常的酸钙体酸性更低，并且缺乏多磷酸盐，但含有可溶性焦磷酸酶。突变体寄生虫在体外是可行的，但无法在小鼠中建立感染，这表明AP 3在确定寄生虫毒力方面的作用-可能通过酸钙体相关功能。AP 3转运功能以前已与溶酶体相关的细胞器，如血小板致密颗粒，这似乎与酸钙体共享几个功能。我们的研究结果，暗示AP 3在运输到酸钙体中具有作用，从而提供了进一步的证据，表明酸钙体的生物发生类似于溶酶体相关的细胞器，并且两者都可能具有保守的起源。
Lysosomal function is crucial for the differentiation and infectivity of the parasitic protozoon Leishmania major. To study lysosomal biogenesis, an L. major mutant deficient in the delta subunit of the adaptor protein 3 (AP3 delta) complex was generated. Structure and proteolytic capacity of the lysosomal compartment were apparently unaffected in the AP3-deficient mutant; however, defects were identified in its acidocalcisomes. These are acidic organelles enriched in calcium and phosphorus, conserved from bacteria to eukaryotes, whose function remains enigmatic. The acidocalcisomes of the L. major mutant lacked membrane-bound proton pumps (notably V-H+-PPase), were less acidic than normal acidocalcisomes and devoid of polyphosphate, but contained a soluble pyrophosphatase. The mutant parasites were viable in vitro, but were unable to establish an infection in mice, which indicates a role for AP3 in determining - possibly through an acidocalcisome-related function - the virulence of the parasite. AP3 transport function has been linked previously to lysosome-related organelles such as platelet dense granules, which appear to share several features with acidocalcisomes. Our findings, implicating that AP3 has a role in transport to acidocalcisomes, thus provide further evidence that biogenesis of acidocalcisomes resembles that of lysosome-related organelles, and that both may have conserved origins.