The Mn-motif protein MAP6d1 assembles ciliary doublet microtubules
Abstract Most eukaryotic cells have cilia that serve vital functions in sensing, signalling, motility. The core architecture of cilia is an array of microtubule doublets, which consist of a complete A-tubule and an incomplete B-tubule. How these structures assemble remains poorly understood. Using t...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61679-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849769140088209408 |
|---|---|
| author | Dharshini Gopal Juliette Wu Julie Delaroche Christophe Bosc Manon De Andrade Eric Denarier Gregory Effantin Annie Andrieux Sylvie Gory-Fauré Laurence Serre Isabelle Arnal |
| author_facet | Dharshini Gopal Juliette Wu Julie Delaroche Christophe Bosc Manon De Andrade Eric Denarier Gregory Effantin Annie Andrieux Sylvie Gory-Fauré Laurence Serre Isabelle Arnal |
| author_sort | Dharshini Gopal |
| collection | DOAJ |
| description | Abstract Most eukaryotic cells have cilia that serve vital functions in sensing, signalling, motility. The core architecture of cilia is an array of microtubule doublets, which consist of a complete A-tubule and an incomplete B-tubule. How these structures assemble remains poorly understood. Using total internal reflection fluorescence microscopy and cryo-electron tomography, we investigate the role of MAP6d1, a brain-specific protein containing microtubule lumen-targeting Mn-motifs. We show that MAP6d1 assembles stable microtubule doublets by recruiting tubulin dimers onto the A-tubule lattice to initiate B-tubule nucleation. MAP6d1 also promotes the formation of luminal protofilaments in singlet and doublet microtubules, a previously undescribed phenomenon that likely enhances microtubule stability. In neurons, MAP6d1 localises to the proximal part of primary cilia via its Mn-motif, with its loss resulting in shortened cilia, a characteristic of ciliopathies. MAP6d1 is thus a neuronal Mn-motif protein with a specific role in assembling microtubule doublets and regulating ciliary length. |
| format | Article |
| id | doaj-art-076dee8a5b674a2682f7b49937e489ae |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-076dee8a5b674a2682f7b49937e489ae2025-08-20T03:03:33ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-61679-0The Mn-motif protein MAP6d1 assembles ciliary doublet microtubulesDharshini Gopal0Juliette Wu1Julie Delaroche2Christophe Bosc3Manon De Andrade4Eric Denarier5Gregory Effantin6Annie Andrieux7Sylvie Gory-Fauré8Laurence Serre9Isabelle Arnal10Grenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesGrenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesGrenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesGrenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesGrenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesGrenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesInstitut de Biologie Structurale (IBS), CNRS, CEA, Université Grenoble AlpesGrenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesGrenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesGrenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesGrenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble AlpesAbstract Most eukaryotic cells have cilia that serve vital functions in sensing, signalling, motility. The core architecture of cilia is an array of microtubule doublets, which consist of a complete A-tubule and an incomplete B-tubule. How these structures assemble remains poorly understood. Using total internal reflection fluorescence microscopy and cryo-electron tomography, we investigate the role of MAP6d1, a brain-specific protein containing microtubule lumen-targeting Mn-motifs. We show that MAP6d1 assembles stable microtubule doublets by recruiting tubulin dimers onto the A-tubule lattice to initiate B-tubule nucleation. MAP6d1 also promotes the formation of luminal protofilaments in singlet and doublet microtubules, a previously undescribed phenomenon that likely enhances microtubule stability. In neurons, MAP6d1 localises to the proximal part of primary cilia via its Mn-motif, with its loss resulting in shortened cilia, a characteristic of ciliopathies. MAP6d1 is thus a neuronal Mn-motif protein with a specific role in assembling microtubule doublets and regulating ciliary length.https://doi.org/10.1038/s41467-025-61679-0 |
| spellingShingle | Dharshini Gopal Juliette Wu Julie Delaroche Christophe Bosc Manon De Andrade Eric Denarier Gregory Effantin Annie Andrieux Sylvie Gory-Fauré Laurence Serre Isabelle Arnal The Mn-motif protein MAP6d1 assembles ciliary doublet microtubules Nature Communications |
| title | The Mn-motif protein MAP6d1 assembles ciliary doublet microtubules |
| title_full | The Mn-motif protein MAP6d1 assembles ciliary doublet microtubules |
| title_fullStr | The Mn-motif protein MAP6d1 assembles ciliary doublet microtubules |
| title_full_unstemmed | The Mn-motif protein MAP6d1 assembles ciliary doublet microtubules |
| title_short | The Mn-motif protein MAP6d1 assembles ciliary doublet microtubules |
| title_sort | mn motif protein map6d1 assembles ciliary doublet microtubules |
| url | https://doi.org/10.1038/s41467-025-61679-0 |
| work_keys_str_mv | AT dharshinigopal themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT juliettewu themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT juliedelaroche themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT christophebosc themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT manondeandrade themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT ericdenarier themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT gregoryeffantin themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT annieandrieux themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT sylviegoryfaure themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT laurenceserre themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT isabellearnal themnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT dharshinigopal mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT juliettewu mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT juliedelaroche mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT christophebosc mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT manondeandrade mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT ericdenarier mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT gregoryeffantin mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT annieandrieux mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT sylviegoryfaure mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT laurenceserre mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules AT isabellearnal mnmotifproteinmap6d1assemblesciliarydoubletmicrotubules |