OSCR

Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2.

Overview

Authors: Matthew J Morris1, Yvonne Y Yeap1,2, Jonathon R Edwards1, Chi Chen1, Annalisa Paolino1, Sebastian G B Furness1, S Sean Millard1, Julia K Pagan1, Laura R Fenlon1,3, Dominic C H Ng1
ORCID iDs: Matthew J Morris, Annalisa Paolino, Sebastian G B Furness, S Sean Millard, Julia K Pagan, Dominic C H Ng
  1. School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4072 Australia
  2. Present Address: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Singapore, 138648 Singapore
  3. Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072 Australia
Institutions: The University of Queensland (Australia); Agency for Science, Technology and Research (Singapore); Singapore Immunology Network (Singapore)
Journal: The EMBO journal, volume 45, issue 7, pages 2157-2181
Dates: received 30 June 2025; accepted 5 February 2026; published online 5 March 2026; in print April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s44318-026-00724-0 · PMID 41787126 · PMCID PMC13043766 · OpenAlex W7133936100
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials, Connectivity, fMRI & imaging, Physiology & signal measures
Keywords: BAG2, Microcephaly, Molecular Chaperones, Purine Metabolism, WDR62, Development, Metabolism, Neuroscience
MeSH: Microcephaly*, Molecular Chaperones*, Nerve Tissue Proteins*, Purines*, Animals, Cell Cycle Proteins, Humans, Mice, Protein Binding (* major topic)
Topic: Microtubule and mitosis dynamics (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Tour de Cure (RSP-079-2024); Department of Education, Australian Government (AusGovEducation) (N/A)
Citations: not cited yet (Europe PMC); 85 references in the paper

Abstract

Inherited mutations in the spindle pole-associated scaffold protein WDR62 cause autosomal recessive primary microcephaly. Previous research has characterised the roles of WDR62 in the regulation of spindle dynamics, cell division, and brain development. Here, we identify a new function of this protein in regulating purine metabolism. WDR62 interacts directly with BAG2, a co-chaperone of HSP70/90. Under stress conditions, WDR62 and BAG2 re-localise to cytoplasmic granules enriched for enzymes involved in purine synthesis (PFAS) and salvage (HPRT). In WDR62-deficient cells, purine synthesis is impaired, while purine deprivation leads to cytotoxicity and nucleoside accumulation. Furthermore, in these cells elevated BAG2 levels are linked to HPRT destabilisation, which can be reversed by BAG2 knockdown. Notably, microcephaly-associated WDR62 mutations disrupt interaction with BAG2 and fail to restore HPRT levels. In utero depletion of WDR62 or HPRT in the mouse neocortex causes premature delamination and migration of neural precursor cells. Interestingly, HPRT loss enhances self-renewal and proliferation of these precursors, contrasting with the reduced proliferation and precocious differentiation observed upon WDR62 loss. Our study identifies regulatory functions of WDR62 in purine metabolism that may contribute to primary microcephaly.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Other data links

Data availability

The mass spectrometry data from this publication have been deposited in the Figshare database (https://figshare.com/) and assigned the identifier 10.6084/m9.figshare.30959294. The BioID dataset for Fig. 1 has also been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD074147 (http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD074147).

The source data of this paper are collected in the following database record: biostudies:S-SCDT-10_1038-S44318-026-00724-0 (https://www.ebi.ac.uk/biostudies/sourcedata/studies/S-SCDT-10_1038-S44318-026-00724-0).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 8 keywords, 9 MeSH terms, 2 funders, 85 references.

Cite

This paper

Morris, M. J., Yeap, Y. Y., Edwards, J. R., Chen, C., Paolino, A., Furness, S. G. B., Millard, S. S., Pagan, J. K., Fenlon, L. R., & Ng, D. C. H. (2026). Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2. The EMBO journal, 45(7), 2157-2181. https://doi.org/10.1038/s44318-026-00724-0

BibTeX

@article{morris2026microcephaly,
author = {Morris, Matthew J and Yeap, Yvonne Y and Edwards, Jonathon R and Chen, Chi and Paolino, Annalisa and Furness, Sebastian G B and Millard, S Sean and Pagan, Julia K and Fenlon, Laura R and Ng, Dominic C H},
title = {{Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2}},
journal = {The EMBO journal},
year = {2026},
month = mar,
volume = {45},
number = {7},
pages = {2157--2181},
publisher = {Nature Publishing Group},
issn = {0261-4189},
doi = {10.1038/s44318-026-00724-0},
url = {https://doi.org/10.1038/s44318-026-00724-0},
pmid = {41787126},
pmcid = {PMC13043766}
}

RIS

TY - JOUR
AU - Morris, Matthew J
AU - Yeap, Yvonne Y
AU - Edwards, Jonathon R
AU - Chen, Chi
AU - Paolino, Annalisa
AU - Furness, Sebastian G B
AU - Millard, S Sean
AU - Pagan, Julia K
AU - Fenlon, Laura R
AU - Ng, Dominic C H
TI - Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2
T2 - The EMBO journal
J2 - EMBO J
PY - 2026
DA - 2026/03/05
VL - 45
IS - 7
SP - 2157
EP - 2181
SN - 0261-4189
PB - Nature Publishing Group
DO - 10.1038/s44318-026-00724-0
UR - https://doi.org/10.1038/s44318-026-00724-0
LA - en
ER -

CSL-JSON

{
"id": "10.1038/s44318-026-00724-0",
"type": "article-journal",
"title": "Microcephaly-associated protein WDR62 supports purine metabolism by interacting with co-chaperone BAG2",
"container-title": "The EMBO journal",
"author": [
{
"family": "Morris",
"given": "Matthew J"
},
{
"family": "Yeap",
"given": "Yvonne Y"
},
{
"family": "Edwards",
"given": "Jonathon R"
},
{
"family": "Chen",
"given": "Chi"
},
{
"family": "Paolino",
"given": "Annalisa"
},
{
"family": "Furness",
"given": "Sebastian G B"
},
{
"family": "Millard",
"given": "S Sean"
},
{
"family": "Pagan",
"given": "Julia K"
},
{
"family": "Fenlon",
"given": "Laura R"
},
{
"family": "Ng",
"given": "Dominic C H"
}
],
"container-title-short": "EMBO J",
"volume": "45",
"issue": "7",
"page": "2157-2181",
"DOI": "10.1038/s44318-026-00724-0",
"PMID": "41787126",
"PMCID": "PMC13043766",
"ISSN": "0261-4189",
"publisher": "Nature Publishing Group",
"URL": "https://doi.org/10.1038/s44318-026-00724-0",
"language": "en",
"issued": {
"date-parts": [
[
2026,
3,
5
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1126/sciadv.aed8653
Targeting astrocytic Dp71 attenuates BBB disruption after traumatic brain injury through WTAP-associated m<sup>6</sup>A regulation of MMP2.
Journal: Science advances
In common: ebi.ac.uk/pdbe/pisa, mouse, cellular / molecular
[2] doi:10.1002/cns.70934
X-Linked USP11 Drives Depression-Like Behaviors by Stabilizing CK2α and Disrupting Mitochondrial Function.
Journal: CNS neuroscience & therapeutics
In common: ebi.ac.uk/pdbe/pisa, mouse, cellular / molecular
[3] doi:10.1016/j.ynstr.2026.100791
USP11 drives stress-induced synaptic structural deficits and depression-like behaviors through GSK3β/mTOR signaling.
Journal: Neurobiology of stress
In common: ebi.ac.uk/pdbe/pisa, mouse, cellular / molecular
[4] doi:10.3892/ijmm.2026.5912
<i>FLI1</i> enhances the malignant phenotype of glioma cells and exerts immunomodulatory effects through feedback crosstalk with exonic circRNA <i>FECR1</i> and interferon‑induced <i>ISG15</i>.
Journal: International journal of molecular medicine
In common: ebi.ac.uk/pdbe/pisa, cellular / molecular
[5] doi:10.1002/adhm.202504889 [code]
Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.
Journal: Advanced healthcare materials
In common: 2 references
[6] doi:10.7554/elife.105935
Uncovering the electrical synapse proteome in retinal neurons via in vivo proximity labeling.
Journal: eLife
In common: mouse, cellular / molecular, 2 references
[7] doi:10.1038/s44318-026-00806-z [code]
Interspecific diversity in the neuronal composition of the mammalian cortex arises from heterochrony in neurogenesis.
Journal: The EMBO journal
In common: 2 references
[8] doi:10.7717/peerj.21426 [code]
Integrated transcriptomic identification and validation reveal key autophagy-associated biomarkers in sleep deprivation.
Journal: PeerJ
In common: mouse, cellular / molecular, 1 reference
[9] doi:10.1038/s44321-026-00427-3
Distinct pathophysiological mechanisms of CEP152 variants in microcephaly and brain abnormalities.
Journal: EMBO molecular medicine
In common: mouse, cellular / molecular, 1 reference
[10] doi:10.1186/s13195-026-02107-3
FKBP51 inhibition by SAFit2 modulates tau pathology and cognitive deficits in PS19 mice.
Journal: Alzheimer's research & therapy
In common: mouse, cellular / molecular, 1 reference

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.