Unconventional secretion of FABP4 by endosomes and secretory lysosomes.

Unconventional secretion of FABP4 by endosomes and secretory lysosomes.
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DOI:
10.1083/jcb.201705047
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发表时间:
2018-02-05
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Schekman R
Schekman R
中科院分区:
其他
文献类型:
--
作者:
Villeneuve J;Bassaganyas L;Lepreux S;Chiritoiu M;Costet P;Ripoche J;Malhotra V;Schekman R

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Adipocytes secrete fatty acid binding protein 4, which influences glucose production in hepatocytes and insulin secretion in pancreatic β-cells, but the mechanisms of its secretion are unclear. Villeneuve et al. show that FABP4 is secreted unconventionally through enclosure within endosomes and secretory lysosomes. An appreciation of the functional properties of the cytoplasmic fatty acid binding protein 4 (FABP4) has advanced with the recent demonstration that an extracellular form secreted by adipocytes regulates a wide range of physiological functions. Little, however, is known about the mechanisms that mediate the unconventional secretion of FABP4. Here, we demonstrate that FABP4 secretion is mediated by a membrane-bounded compartment, independent of the conventional endoplasmic reticulum–Golgi secretory pathway. We show that FABP4 secretion is also independent of GRASP proteins, autophagy, and multivesicular bodies but involves enclosure within endosomes and secretory lysosomes. We highlight the physiological significance of this pathway with the demonstration that an increase in plasma levels of FABP4 is inhibited by chloroquine treatment of mice. These findings chart the pathway of FABP4 secretion and provide a potential therapeutic means to control metabolic disorders associated with its dysregulated secretion.
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影响因子: --
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