2026-06-25 ミュンヘン大学（LMU）
＜関連情報＞
- https://www.lmu.de/en/newsroom/news-overview/news/brain-development-when-cytoskeletal-proteins-act-in-the-cell-nucleus-f6c260d7.html
- https://www.cell.com/cell/fulltext/S0092-8674(26)00578-7
核プロテオーム解析により、細胞の運命と疾患を制御する微小管関連タンパク質が明らかになった Nuclear proteome reveals microtubule-associated protein regulating fate and disease
Florencia Merino ∙ Lucas Miranda ∙ Aparajita Kumar ∙ … ∙ Stefanie M. Hauck ∙ Silvia Cappello ∙ Magdalena Götz
Cell Published:June 11, 2026
DOI:https://doi.org/10.1016/j.cell.2026.05.019
Graphical abstract
Highlights
- Nuclear and cytosolic proteomics reveal widespread nuclear cytoskeletal proteins
- MAP1B shuttles between compartments in NSCs and impacts differentiation
- MAP1B interacts with the BAF chromatin-remodeling complex in the nucleus
- Disease-linked mutated MAP1B shows nuclear enrichment and increased BRG1/BAF binding
Summary
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.
