» Articles » PMID: 29212659

Unconventional Secretion of FABP4 by Endosomes and Secretory Lysosomes

Overview
Journal J Cell Biol
Specialty Cell Biology
Date 2017 Dec 8
PMID 29212659
Citations 45
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

The pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network.

Curwin A, Kurokawa K, Bigliani G, Brouwers N, Nakano A, Malhotra V J Cell Biol. 2025; 224(5).

PMID: 40015244 PMC: 11867701. DOI: 10.1083/jcb.202312120.


Molecular mechanisms and pathological implications of unconventional protein secretion in human disease: from cellular stress to therapeutic targeting.

Liu Y, Zhang H, Li X, He T, Zhang W, Ji C Mol Biol Rep. 2025; 52(1):236.

PMID: 39955475 DOI: 10.1007/s11033-025-10316-6.


Canonical and noncanonical autophagy: involvement in Parkinson's disease.

Sakurai M, Kuwahara T Front Cell Dev Biol. 2025; 13:1518991.

PMID: 39949604 PMC: 11821624. DOI: 10.3389/fcell.2025.1518991.


Cancer cells avoid ferroptosis induced by immune cells via fatty acid binding proteins.

Freitas-Cortez M, Masrorpour F, Jiang H, Mahmud I, Lu Y, Huang A Mol Cancer. 2025; 24(1):40.

PMID: 39901247 PMC: 11789333. DOI: 10.1186/s12943-024-02198-2.


Endocytic tethers modulate unconventional GAPDH secretion.

Cohen M, Philippe B, Lipke P Cell Surf. 2025; 13():100138.

PMID: 39830088 PMC: 11742311. DOI: 10.1016/j.tcsw.2024.100138.


References
1.
BERNSTEIN H . Ocular safety of hydroxychloroquine. Ann Ophthalmol. 1991; 23(8):292-6. View

2.
Rodriguez A, Webster P, Ortego J, Andrews N . Lysosomes behave as Ca2+-regulated exocytic vesicles in fibroblasts and epithelial cells. J Cell Biol. 1997; 137(1):93-104. PMC: 2139854. DOI: 10.1083/jcb.137.1.93. View

3.
Marsh M, McMahon H . The structural era of endocytosis. Science. 1999; 285(5425):215-20. DOI: 10.1126/science.285.5425.215. View

4.
Bowman E, Siebers A, Altendorf K . Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc Natl Acad Sci U S A. 1988; 85(21):7972-6. PMC: 282335. DOI: 10.1073/pnas.85.21.7972. View

5.
Mambula S, Calderwood S . Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes. J Immunol. 2006; 177(11):7849-57. DOI: 10.4049/jimmunol.177.11.7849. View