PIKfyve regulates melanosome biogenesis.
PIKfyve regulates melanosome biogenesis.
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DOI：
10.1371/journal.pgen.1007290
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发表时间：
2018-03
期刊：
影响因子：
4.5
通讯作者：
Ganesan AK
中科院分区：
文献类型：
--
作者：
Liggins MC;Flesher JL;Jahid S;Vasudeva P;Eby V;Takasuga S;Sasaki J;Sasaki T;Boissy RE;Ganesan AK
PIKfyve、VAC14和FIG4形成一个复合体，催化PI(3，5)P2的产生，PI(3，5)P2是一种信号脂质，参与从溶酶体成熟到神经退化的一系列过程。虽然之前的研究已经发现VAC14和FIG4突变会导致神经退化和毛色缺陷，但PIKfyve如何调控黑素生成尚不清楚。在这项研究中，我们试图更好地了解PIKfyve在黑素小体生物发生中的作用。黑素细胞特异性PIKfyve基因敲除小鼠的皮毛变灰，黑素细胞中单膜囊泡结构积聚，类似于多囊内小体。PIKfyve抑制抑制黑素小体成熟、黑素小体蛋白PMEL的加工和黑素小体蛋白TYRP1的运输。综上所述，这些研究确定了PIKfyve在控制蛋白质从内小体运送到黑素体中的新角色，这一角色不同于PIKfyve在内溶酶体重组溶酶体中的作用。为了使细胞发育和维持功能细胞器，蛋白质必须以精确、顺序的方式输送到发育中的细胞器。在这项研究中，我们使用一个成熟的细胞器生物发生(黑素小体)模型来了解肌醇磷脂是如何调节囊泡运输和黑素生成的。阻断PI(3，5)P2的合成会抑制黑素小体的成熟，并诱导多囊泡内小体的积累。有趣的是，这种作用不同于PI(3，5)P2在溶酶体重塑中的作用。综上所述，这些研究确定了PI(3，5)P2在黑素体生物发生中的不同作用。
PIKfyve, VAC14, and FIG4 form a complex that catalyzes the production of PI(3,5)P2, a signaling lipid implicated in process ranging from lysosome maturation to neurodegeneration. While previous studies have identified VAC14 and FIG4 mutations that lead to both neurodegeneration and coat color defects, how PIKfyve regulates melanogenesis is unknown. In this study, we sought to better understand the role of PIKfyve in melanosome biogenesis. Melanocyte-specific PIKfyve knockout mice exhibit greying of the mouse coat and the accumulation of single membrane vesicle structures in melanocytes resembling multivesicular endosomes. PIKfyve inhibition blocks melanosome maturation, the processing of the melanosome protein PMEL, and the trafficking of the melanosome protein TYRP1. Taken together, these studies identify a novel role for PIKfyve in controlling the delivery of proteins from the endosomal compartment to the melanosome, a role that is distinct from the role of PIKfyve in the reformation of lysosomes from endolysosomes. In order for a cell to develop and maintain functional organelles, proteins must be delivered to developing organelles in a precise, sequential fashion. In this study, we used a well-established model for organelle biogenesis (the melanosome) to understand how phosphoinositides regulate vesicle trafficking and melanogenesis. Blocking PI(3,5)P2 synthesis inhibits melanosome maturation and induces the accumulation of multivesicular endosomes. Intriguingly, this role is different from the role of PI(3,5)P2 in lysosomal reformation. Taken together, these studies identify distinct roles for PI(3,5)P2 in melanosome biogenesis.
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影响因子：
16.6
作者：
Dong, Xian-ping;Shen, Dongbiao;Wang, Xiang;Dawson, Taylor;Li, Xinran;Zhang, Qi;Cheng, Xiping;Zhang, Yanling;Weisman, Lois S.;Delling, Markus;Xu, Haoxing
通讯作者：
Xu, Haoxing
DOI：
10.1111/j.1600-0854.2009.00915.x
发表时间：
2009-07
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
de Lartigue J;Polson H;Feldman M;Shokat K;Tooze SA;Urbé S;Clague MJ
通讯作者：
Clague MJ
影响因子：
11.4
作者：
Kerr, Markus C.;Wang, Jack T. H.;Teasdale, Rohan D.
通讯作者：
Teasdale, Rohan D.
影响因子：
4.5
作者：
Bissig, Christin;Hurbain, Ilse;van Niel, Guillaume
通讯作者：
van Niel, Guillaume
DOI：
10.1073/pnas.1600108113
发表时间：
2016-05-17
影响因子：
11.1
作者：
Ambrosio, Andrea L.;Boyle, Judith A.;Di Pietro, Santiago M.
通讯作者：
Di Pietro, Santiago M.