PXD046646-2

PXD046646 is an original dataset announced via ProteomeXchange.

Title	Proteomic Landscape of Endoplasmic Reticulum Remodeling During Neurogenesis via Combinatorial Selective ER-phagy
Description	The endoplasmic reticulum (ER) functions in protein and lipid synthesis, calcium ion flux, and inter-organelle communication, all of which are driven by the ER proteome landscape. ER is remodeled in part through autophagy-dependent protein turnover involving membrane-embedded ER-phagy receptors1,2. A refined tubular ER network is formed in neurons within highly polarized dendrites and axons3,4. Autophagy-deficient neurons in vivo display axonal ER accumulation within synaptic ER boutons, associated with hyper-excitability,5 and the ER-phagy receptor FAM134B has been genetically linked with human sensory and autonomic neuropathy6,7. However, mechanisms and receptor selectivity underlying ER remodeling by autophagy in neurons is limited. Here, we employ genetic, proteomic and computational tools to create a quantitative landscape of ER proteome remodeling via selective autophagy during conversion of stem cells to induced neurons in vitro. Through analysis of single and combinatorial ER-phagy receptor mutants coupled with an allelic series computational framework, we delineate the extent to which each of five receptors contributes to both the magnitude of ER turnover by autophagy and the selectivity of clearance for individual ER proteins. We define specific subsets of reticulon-domain containing ER-tubule shaping proteins or luminal proteins as preferred clients for autophagic turnover via distinct receptors. Using spatial sensors and flux reporters, we demonstrate receptor-specific autophagic capture of ER in axons, which correlates with aberrant accumulation of ER in axonal structures in ER-phagy receptor or autophagy-deficient cells. This molecular inventory of ER proteome remodeling and versatile genetic toolkit provides a quantitative framework for understanding the contributions of individual ER-phagy receptors for reshaping this critical organelle during transitions in cell states.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:19:39.301.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Melissa Hoyer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-03 07:51:41	ID requested
1	2024-01-08 11:56:49	announced
⏵ 2	2024-10-22 06:19:39	announced	2024-10-22: Updated project metadata.
⏵ 2	2024-10-22 06:19:39	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: selective autophagy, ER-phagy, human induced neurons,TMT 18-plex

Jeffrey Wade Harper
contact affiliation	Department of Cell Biology, Harvard Medical School, Boston MA 02115
contact email	wade_harper@hms.harvard.edu
lab head
Melissa Hoyer
contact affiliation	Harvard Medical School
contact email	melissa_hoyer@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046646
     1. Label: PRIDE project
     2. Name: Proteomic Landscape of Endoplasmic Reticulum Remodeling During Neurogenesis via Combinatorial Selective ER-phagy