Dataset Information

MTORC1 regulates GRASP55-dependent unconventional secretion in response to stress

ABSTRACT: In cells, several cargoes are delivered to the cell surface or the extracellular space via unconventional secretion routes. GRASP55 is a Golgi protein that regulates unconventional secretion of distinct proteins and controls the assembly and membrane stacking of Golgi cisternae. Recent work suggested that the role of GRASP55 in unconventional secretion may involve its relocalization to other organelles. However, the stimuli that drive GRASP55-dependent unconventional secretion, the signaling events that regulate GRASP55 function, the subcellular locations where GRASP55 acts, and the cargoes that follow this route for secretion remain unclear. Here, we show that mTORC1 directly phosphorylates GRASP55 at multiple sites to maintain its Golgi localization. Cellular stresses or drugs that inhibit mTORC1 cause GRASP55 dephosphorylation and relocalization to autophagosomal / MVB structures. Using secretome and surfactome analyses in GRASP55-null cells, we identify for the first time numerous -previously unknown- cargoes that rely on this unconventional secretory pathway.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryonic Cell, Cell Culture, Fibroblast

SUBMITTER: Janica Wiederstein

LAB HEAD: Markus Plomann

PROVIDER: PXD020331 | Pride | 2021-09-09

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20180622_Q1_AWH_ColID_586_ProjID_1255_Paulssen_sample_1.raw	Raw
	20180622_Q1_AWH_ColID_586_ProjID_1255_Paulssen_sample_2.raw	Raw
	20180622_Q1_AWH_ColID_586_ProjID_1255_Paulssen_sample_3.raw	Raw
	20180622_Q1_AWH_ColID_586_ProjID_1255_Paulssen_sample_4.raw	Raw
	20180622_Q1_AWH_ColID_586_ProjID_1255_Paulssen_sample_5.raw	Raw

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Publications

An mTORC1-GRASP55 signaling axis controls unconventional secretion to reshape the extracellular proteome upon stress.

Nüchel Julian J Tauber Marina M Nolte Janica L JL Mörgelin Matthias M Türk Clara C Eckes Beate B Demetriades Constantinos C Plomann Markus M

Molecular cell 20210709 16

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, ...[more]

PMID: 34245671

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