PXD055950-1

PXD055950 is an original dataset announced via ProteomeXchange.

Title	The membrane curvature-inducing REEP1-4 proteins generate an ER-derived vesicular compartment
Description	The endoplasmic reticulum (ER) is shaped by abundant membrane curvature-generating proteins that include the REEP family member REEP5. The REEP1 subfamily, consisting of REEP1-4 in mammals, is less abundant and lacks a N-terminal region. Mutations in REEP1 and REEP2 cause Hereditary Spastic Paraplegia, but REEP1-4's function remains enigmatic. Here we show that REEP1-4 reside in a unique vesicular compartment and identify features that determine their localization. Mutations in REEP1-4 that compromise curvature generation, including those causing disease, relocalize the proteins to the bulk ER. These mutants interact with wild-type proteins to retain them in the ER, consistent with their autosomal-dominant disease inheritance. REEP1 vesicles contain the membrane fusogen atlastin-1, but not general ER proteins. We propose that REEP1-4 generate these vesicles themselves by budding from the ER, and that they cycle back to the ER by atlastin-mediated fusion. The vesicles may serve to regulate ER tubule dynamics.
HostingRepository	PRIDE
AnnounceDate	2025-01-18
AnnouncementXML	Submission_2025-01-17_19:50:23.064.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; carbamoylated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-17 12:51:55	ID requested
⏵ 1	2025-01-17 19:50:23	announced

10.1038/s41467-024-52901-6;

Shibata Y, Mazur EE, Pan B, Paulo JA, Gygi SP, Chavan S, Valerio LSA, Zhang J, Rapoport TA, The membrane curvature-inducing REEP1-4 proteins generate an ER-derived vesicular compartment. Nat Commun, 15(1):8655(2024) [pubmed]

submitter keyword: REEP5, REEP1,Endoplasmic reticulum, membrane curvature, tubules, vesicles, hereditary spastic paraplegia

Tom A. Rapoport
contact affiliation	Howard Hughes Medical Institute and Department of Cell Biology Harvard Medical School 240 Longwood Avenue Boston, Massachusetts 02115, USA
contact email	tom_rapoport@hms.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055950
     1. Label: PRIDE project
     2. Name: The membrane curvature-inducing REEP1-4 proteins generate an ER-derived vesicular compartment