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Merino, F.L. ; Miranda, L.* ; Kumar, A. ; Li, Y. ; Kumar Sundaramoorthy, D. ; Merl-Pham, J. ; Schentarra, E.M.* ; Steinek, C.* ; Pravata, V.* ; Kittock, C.* ; Bürkle, M. ; Hersbach, B.A. ; Ferri Beneito, J. ; Giesert, F. ; Jungmann, R.* ; Pilaz, L.J.* ; Hauck, S.M. ; Cappello, S. ; Götz, M.

Nuclear proteome reveals microtubule-associated protein regulating fate and disease.

Cell 189, 5026-5043 (2026)
Publ. Version/Full Text Research data DOI
Open Access Hybrid
Creative Commons Lizenzvertrag
Cellular differentiation and morphogenesis require the coordination between cytoskeletal remodeling and transcriptional programs, raising the question of how cytoskeletal information is conveyed to the nucleus. Here, we profile the nuclear and cytosolic proteome of human and murine neural stem cells (NSCs) and uncover abundant cytoskeletal proteins in the nucleus, including the microtubule-associated protein 1B (MAP1B), implicated in disease. We find that MAP1B shuttles to the nucleus where it interacts with the BRG1-containing chromatin remodeling complex. MAP1B’s nuclear enrichment promotes NSC fate, as opposed to its cytosolic function promoting neuronal differentiation. In vivo , increasing the nuclear/cytosol ratio disrupts neuronal positioning, reminiscent of patients with MAP1B mutations. Mutant human brain organoids show aberrant MAP1B nuclear enrichment, enhanced BRG1 chromatin binding, and neuronal ectopia formation. Our study uncovers a nuclear pool of cytoskeleton-associated proteins, revealing their role in fate regulation during brain development and reshaping our understanding of neurodevelopmental disease etiology.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Brain Development ; Cell Fate ; Cortical Malformations ; Map1b ; Migration ; Moonlighting Proteins ; Neural Stem Cells ; Neurogenesis ; Organoids ; Periventricular Heterotopia; Neuronal Migration; Cytoskeletal Proteins; Cerebral Organoids; Stem-cells; Web Server; Map1b; Actin; Transcription; Maintenance; Differentiation
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 189, Issue: 16, Pages: 5026-5043 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
Core Facility Metabolomics and Proteomics (CF-MPC)
Grants New Frontiers in Research Fund Transformation grant through SSHRC
New Frontiers in Research Fund Transformation grant through NSERC
New Frontiers in Research Fund Transformation grant through CIHR
European Union
German Excellence Cluster SyNergy
European Research Council