Proteomics

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


ABSTRACT: Tunneling NanoTubes (TNTs) are membrane conduits that mediate long distance intercellular crosstalk 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 is essential for TNT formation in multiple cell types. We identified a novel interaction of MSec with the endoplasmic reticulum chaperone ERp29. ERp29 depletion in mammalian cells led to a significant reduction in TNT formation, while its over-expression induced TNT formation, but strictly in an 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. Our study implicates MSec as a new target of ERp29 and reveals an indispensable role for the endoplasmic reticulum in the biogenesis of TNTs, thus suggesting new modalities for regulating TNT numbers.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Bone Marrow

DISEASE(S): Osteosarcoma

SUBMITTER: Sivaram Mylavarapu  

LAB HEAD: Sivaram V S Mylavarapu

PROVIDER: PXD012441 | Pride | 2019-03-15

REPOSITORIES: Pride

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

Pergu Rajaiah R   Dagar Sunayana S   Kumar Harsh H   Kumar Rajesh R   Bhattacharya Jayanta J   Mylavarapu Sivaram V S SVS  

The Journal of biological chemistry 20190315 18


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 identifi  ...[more]

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