The chaperone ERp29 is required for tunneling nanotube formation by stabilizing MSec

Pergu, Rajaiah and Kumar, Harsha and Mylavarapu, Sivaram VS (2019) The chaperone ERp29 is required for tunneling nanotube formation by stabilizing MSec. Journal of Biological Chemistry, 3 (294). pp. 1-30. ISSN 0021-9258

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Abstract

Tunneling nanotubes (TNTs) are membrane conduits that mediate long distance intercellular cross-talk in several organisms and play vital roles during development, pathogenic transmission, and cancer metastasis. However, the molecular mechanisms of TNT formation and function remain poorly understood. The protein MSec (also known as TNFα-induced protein 2 (TNFAIP2) and B94) is essential for TNT formation in multiple cell types. Here, using affinity protein purification, mass spectrometric identification, and confocal immunofluorescence microscopy assays, we found that MSec interacts with the endoplasmic reticulum (ER) chaperone ERp29. siRNA-mediated ERp29 depletion in mammalian cells significantly reduces TNT formation, whereas its overexpression induces TNT formation, but in a strictly MSec-dependent manner. ERp29 stabilized MSec protein levels, but not its mRNA levels, and the chaperone activity of ERp29 was required for maintaining MSec protein stability. Subcellular ER fractionation and subsequent limited proteolytic treatment suggested that MSec is associated with the outer surface of the ER. The ERp29-MSec interaction appeared to require the presence of other bridging protein(s), perhaps triggered by post-translational modification of ERp29. Our study implicates MSec as a target of ERp29 and reveals an indispensable role for the ER in TNT formation, suggesting new modalities for regulating TNT numbers in cells and tissues.

Item Type: Article
Uncontrolled Keywords: MSec; TNFα-induced protein 2 (TNAIP2); cell-cell interaction; chaperone; endoplasmic reticulum; endoplasmic reticulum (ER); endoplasmic reticulum protein 29 (ERP29); interactome; intercellular communication; plasma membrane; post-translational modification (PTM); protein stability; protein-disulfide isomerase; tunneling nanotubes.
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 24 Jan 2020 14:03
Last Modified: 24 Jan 2020 14:03
URI: http://eprints.manipal.edu/id/eprint/154776

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