PXD046036

PXD046036 is an original dataset announced via ProteomeXchange.

Title	Localized synthesis of molecular chaperones sustains neuronal proteostasis
Description	Proteostasis at neuronal projections supports the molecular basis behind long-term information storage and movement control. It is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. Using high-resolution fluorescent microscopy, we discovered that neurons localize a subset of chaperone mRNAs to their dendrites and increase this asymmetric localization following proteotoxic stress. The most abundant chaperone mRNA in dendrites encodes for the constitutive heat shock protein 70, HSPA8. Most Hspa8 mRNAs travel in dendrites as single molecules. In the dendrites, Hspa8 mRNAs are locally translated by mono and polyribosomes, and proteotoxic stress further enhances the percentage of mRNAs engaged in translation and their efficiency. We discovered that Fused in Sarcoma (FUS) and heterogenous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) participate in stress-mediated localization of Hspa8 mRNA in dendrites of mouse and human motor neurons, respectively. As such, FUS knocked down neurons accumulate misfolded proteins in dendrites upon stress exposure. Together, these results reveal a novel mechanism allowing neurons to uphold proteostasis at dendrites and spines upon stress.
HostingRepository	PRIDE
AnnounceDate	2024-11-13
AnnouncementXML	Submission_2024-11-13_06:29:06.356.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lokha Ranjani Alagar Boopathy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-10 10:13:05	ID requested
⏵ 1	2024-11-13 06:29:06	announced

Dataset with its publication pending

submitter keyword: HSP/neurons/proteostasis/smFISH/mRNA/stress

Maria Vera Ugalde
contact affiliation	Assistant Professor Department of Biochemistry Montreal, Quebec H3G 1Y6
contact email	maria.veraugalde@mcgill.ca
lab head
Lokha Ranjani Alagar Boopathy
contact affiliation	McGill University
contact email	lokha.alagarboopathy@mail.mcgill.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046036
     1. Label: PRIDE project
     2. Name: Localized synthesis of molecular chaperones sustains neuronal proteostasis