Universität zu Köln

Nuechel, Julian, Tauber, Marina, Nolte, Janica L., Moergelin, Matthias, Tuerk, Clara, Eckes, Beate, Demetriades, Constantinos ORCID: 0000-0001-7813-7726 and Plomann, Markus (2021). An mTORC1-GRASP55 signaling axis controls unconventional secretion to reshape the extracellular proteome upon stress. Mol. Cell, 81 (16). S. 3275 - 3307. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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Abstract

Cells communicate with their environment via surface proteins and secreted factors. Unconventional protein secretion (UPS) is an evolutionarily conserved process, via which distinct cargo proteins are secreted upon stress. Most UPS types depend upon the Golgi-associated GRASP55 protein. However, its regulation and biological role remain poorly understood. Here, we show that the mechanistic target of rapamycin complex 1 (mTORC1) directly phosphorylates GRASP55 to maintain its Golgi localization, thus revealing a physiological role for mTORC1 at this organelle. Stimuli that inhibit mTORC1 cause GRASP55 dephosphorylation and relocalization to UPS compartments. Through multiple, unbiased, proteomic analyses, we identify numerous cargoes that follow this unconventional secretory route to reshape the cellular secretome and surfactome. Using MMP2 secretion as a proxy for UPS, we provide important insights on its regulation and physiological role. Collectively, our findings reveal the mTORC1-GRASP55 signaling hub as the integration point in stress signaling upstream of UPS and as a key coordinator of the cellular adaptation to stress.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nuechel, Julian UNSPECIFIED UNSPECIFIED UNSPECIFIED Tauber, Marina UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Janica L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moergelin, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Tuerk, Clara UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Demetriades, Constantinos UNSPECIFIED orcid.org/0000-0001-7813-7726 UNSPECIFIED Plomann, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-575745
DOI:	10.1016/j.molcel.2021.06.017
Journal or Publication Title:	Mol. Cell
Volume:	81
Number:	16
Page Range:	S. 3275 - 3307
Date:	2021
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4164
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AMINO-ACID STARVATION; GOLGI LOCALIZATION; CELL-GROWTH; S6 KINASE; COMPLEX; MTOR; GRASP; PROTEINS; PATHWAY; DOMAIN Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57574