TTC17 is an endoplasmic reticulum resident TPR-containing adaptor protein.

Autor:	Canniff NP; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, USA., Graham JB; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, USA., Guay KP; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, USA., Lubicki DA; Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, USA., Eyles SJ; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, USA; Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, USA; Institute for Applied Life Sciences, Mass Spectrometry Center, University of Massachusetts Amherst, USA., Rauch JN; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, USA; Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, USA., Hebert DN; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, USA; Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, USA. Electronic address: dhebert@biochem.umass.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2023 Dec; Vol. 299 (12), pp. 105450. Date of Electronic Publication: 2023 Nov 08.
DOI:	10.1016/j.jbc.2023.105450
Abstrakt:	Protein folding, quality control, maturation, and trafficking are essential processes for proper cellular homeostasis. Around one-third of the human proteome is targeted to the endoplasmic reticulum (ER), the organelle that serves as entrance into the secretory pathway. Successful protein trafficking is paramount for proper cellular function and to that end there are many ER resident proteins that ensure efficient secretion. Here, biochemical and cell biological analysis was used to determine that TTC17 is a large, soluble, ER-localized protein that plays an important role in secretory trafficking. Transcriptional analysis identified the predominantly expressed protein isoform of TTC17 in various cell lines. Further, TTC17 localizes to the ER and interacts with a wide variety of chaperones and cochaperones normally associated with ER protein folding, quality control, and maturation processes. TTC17 was found to be significantly upregulated by ER stress and through the creation and use of TTC17 -/- cell lines, quantitative mass spectrometry identified secretory pathway wide trafficking defects in the absence of TTC17. Notably, trafficking of insulin-like growth factor type 1 receptor, glycoprotein nonmetastatic melanoma protein B, clusterin, and UDP-glucose:glycoprotein glucosyltransferase 1 were significantly altered in H4 neuroglioma cells. This study defines a novel ER trafficking factor and provides insight into the protein-protein assisted trafficking in the early secretory pathway. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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