Trafficking of a multifunctional protein by endosomal micro-autophagy: linking two independent unconventional secretory pathways.

Chauhan, Anoop Singh and Kumar, Manoj and Chaudhary, Surbhi and Dhiman, Asmita and Patidar, Anil and Jakhar, Priyanka and Jaswal, Pallavi and Sharma, Kapil and Sheokand, Navdeep and Malhotra, Himanshu and Raje, Chaaya Iyengar and Raje, Manoj (2019) Trafficking of a multifunctional protein by endosomal micro-autophagy: linking two independent unconventional secretory pathways. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. fj201802102R. ISSN 1530-6860

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Official URL: https://www.fasebj.org/doi/abs/10.1096/fj.20180210...

Abstract

During physiologic stresses, like micronutrient starvation, infection, and cancer, the cytosolic moonlighting protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is trafficked to the plasma membrane (PM) and extracellular milieu (ECM). Our work demonstrates that GAPDH mobilized to the PM, and the ECM does not utilize the classic endoplasmic reticulum-Golgi route of secretion; instead, it is first selectively translocated into early and late endosomes from the cytosol via micro-autophagy. GAPDH recruited to this common entry point is subsequently delivered into multivesicular bodies, leading to its membrane trafficking through secretion via exosomes and secretory lysosomes. We present evidence that both pathways of GAPDH membrane trafficking are up-regulated upon iron starvation, potentially by mobilization of intracellular calcium. These pathways also play a role in clearance of misfolded intracellular polypeptide aggregates. Our findings suggest that cells build in redundancy for vital cellular pathways to maintain micronutrient homeostasis and prevent buildup of toxic intracellular misfolded protein refuse.-Chauhan, A. S., Kumar, M., Chaudhary, S., Dhiman, A., Patidar, A., Jakhar, P., Jaswal, P., Sharma, K., Sheokand, N., Malhotra, H., Raje, C. I., Raje. M. Trafficking of a multifunctional protein by endosomal micro-autophagy: linking two independent unconventional secretory pathways.

Item Type: Article
Additional Information: Copyright of this article belongs to Federation of American Societies for Experimental Biology
Uncontrolled Keywords: GAPDH; exosomal exocytosis; lysosomal exocytosis; misfolded protein aggregate; nonclassical protein secretion
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 18 Mar 2019 12:45
Last Modified: 18 Mar 2019 12:45
URI: http://crdd.osdd.net/open/id/eprint/2179

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