PXD046667

PXD046667 is an original dataset announced via ProteomeXchange.

Title	Glycolytic enzyme aldolase A is necessary for reelin mediated neurite growth and arborization
Description	Reelin is a large, secreted glycoprotein that is best known as an essential molecule directing neocortical neuronal migration, but reelin serves an important functional role in regulating neurite outgrowth and arborization as well. Canonically, reelin signals through the lipoprotein receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR). Reelin can signal through non-canonical receptors and unidentified co-receptors as well, but the downstream effects of these non-canonical pathways are not well understood. Using an unbiased Tandem Mass Tag LC-MS/MS (TMT) proteomics screen and gene set enrichment analysis (GSEA), we identified overlapping and distinct intra-cellular pathways enriched downstream of canonical and non-canonical reelin signaling in primary murine neurons during periods of robust neurite arborization. We observed canonical signaling led to substantial changes in actin cytoskeletal dynamics and cell morphogenesis while non-canonical signaling preferentially regulated protein translation, suggesting reelin fine tunes neuronal structure and function through distinct signaling pathways. We also identified a novel node downstream of canonical reelin signaling, glycolytic enzyme and actin binding protein aldolase A (aldo A). Biochemical analysis revealed aldo A undergoes de novo translation and is dissociated from the actin cytoskeleton after acute reelin stimulation. Additionally, shRNA knockdown of aldo A in primary murine cultures and in vivo through in utero electroporation (IUE), reveal aldo A is necessary for reelin mediated neurite growth and the proper arborization and positioning of excitatory layer II/III neurons independent of glycolytic function. These results shed new light on the molecular mechanisms and signaling pathways regulating reelin dependent neuronal arborization.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_11:59:29.224.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	WEIWEI LIN
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-04 09:46:52	ID requested
⏵ 1	2025-05-06 11:59:30	announced

10.1523/jneurosci.0072-24.2024;

Lagani GD, Sha M, Lin W, Natarajan S, Kankkunen M, Kistler SA, Lampl N, Waxman H, Harper ER, Emili A, Beffert U, Ho A, Beyond Glycolysis: Aldolase A Is a Novel Effector in Reelin-Mediated Dendritic Development. J Neurosci, 44(42):(2024) [pubmed]

submitter keyword: LC-MS

Proteomics

Aldolase A

Reelin

Neurite growth

Andrew Emili
contact affiliation	Boston University
contact email	aemili@bu.edu
lab head
WEIWEI LIN
contact affiliation	Boston Univeristy School of Medicine
contact email	linww@bu.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD046667

PRIDE project URI

• PRIDE
  1. PXD046667
     1. Label: PRIDE project
     2. Name: Glycolytic enzyme aldolase A is necessary for reelin mediated neurite growth and arborization