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TitleThe Mn-motif protein MAP6d1 assembles ciliary doublet microtubules.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 6210, Year 2025
Publish dateJul 5, 2025
AuthorsDharshini Gopal / Juliette Wu / Julie Delaroche / Christophe Bosc / Manon De Andrade / Eric Denarier / Gregory Effantin / Annie Andrieux / Sylvie Gory-Fauré / Laurence Serre / Isabelle Arnal /
PubMed AbstractMost 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 ...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.
External linksNat Commun / PubMed:40617876 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution12.5 - 33.0 Å
Structure data

EMDB-52569: MAP6d1 assembles protofilaments in the microtubule lumen
Method: EM (subtomogram averaging) / Resolution: 12.5 Å

EMDB-52572: MAP6d1 assembles protofilaments in the lumen of microtubule doublets
Method: EM (subtomogram averaging) / Resolution: 33.0 Å

EMDB-52574: MAP6d1 assembles microtubule doublets
Method: EM (subtomogram averaging) / Resolution: 22.0 Å

EMDB-52575: MAP6d1 assembles microtubule doublets
Method: EM (subtomogram averaging) / Resolution: 16.0 Å

EMDB-52623: MAP6d1 assembles microtubule doublets
Method: EM (subtomogram averaging) / Resolution: 17.0 Å

EMDB-53452: luminal protofilaments after masked refinement in a singlet microtubule
Method: EM (subtomogram averaging) / Resolution: 21.0 Å

EMDB-53454: Singlet microtubule after masked refinement.
Method: EM (subtomogram averaging) / Resolution: 12.5 Å

EMDB-53457: Combined map of singlet microtubule with 2 luminal protofilament
Method: EM (subtomogram averaging) / Resolution: 12.5 Å

Source
  • Bos taurus (domestic cattle)
  • Mus musculus (house mouse)

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