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Human Secretome Dependence on the Signal Recognition Particle

ABSTRACT: The signal recognition particle (SRP) is a ribonucleoprotein complex responsible for targeting secretory and membrane proteins to the endoplasmic reticulum (ER). SRP co-translationally recognizes secretory proteins via N-terminal signal sequences. SRP-independent protein targeting is also known. When SRP is not able to recognize signal peptides of SRP-dependent proteins (due to mutations, for instance), they do not become SRP-independent; instead, their mRNAs are degraded in the protein quality control RAPP. However, which proteins are SRP-dependent and SRP-independent, especially in mammals, is not known yet. In this work, we answer this fundamental question by mass spec and whole proteome analysis in SRP54 depleted human cells and medium. The analysis shows that the majority of secretory proteins in the medium have lower abundance, demonstrating their SRP dependence. Moreover, we identified new SRP-independent proteins as well. Surprisingly, detailed examination did not elucidate obvious differences of the SRP-dependent and SRP-independent proteins, suggesting other factors regulate this process. We also detect changes in the abundance of proteins that may be involved in the RAPP mechanism and in stress that is associated with defective SRP. Our study demonstrates the complexity of molecular mechanisms of protein sorting and quality control in human cells.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Andrey L. Karamyshev, Ph.D.

PROVIDER: MSV000094747 | MassIVE | Mon May 13 11:09:00 BST 2024

SECONDARY ACCESSION(S): PXD052230

REPOSITORIES: MassIVE

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