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The Mn-motif protein MAP6d1 assembles ciliary doublet microtubules
Dharshini Gopal1, Juliette Wu1, Julie Delaroche1
1Grenoble Institut Neurosciences (GIN), INSERM, U1216, CNRS, CEA, Université Grenoble Alpes, Grenoble, France.
Nature Communications
|July 5, 2025
Summary
MAP6d1, a brain-specific protein, is crucial for assembling stable microtubule doublets in cilia. Its loss leads to shortened cilia, a hallmark of ciliopathies, highlighting its role in ciliary length regulation.
Area of Science:
- Cell Biology
- Neuroscience
- Structural Biology
Background:
- Cilia are vital eukaryotic organelles involved in sensing, signaling, and motility.
- Cilia's core structure comprises microtubule doublets (A-tubule and B-tubule), whose assembly mechanism is not fully understood.
- Microtubule-associated proteins (MAPs) play critical roles in microtubule structure and function.
Purpose of the Study:
- To investigate the role of MAP6d1, a brain-specific protein with microtubule lumen-targeting Mn-motifs, in the assembly of ciliary microtubule doublets.
- To elucidate the mechanism by which MAP6d1 influences microtubule structure and ciliary length.
Main Methods:
- Total internal reflection fluorescence microscopy (TIR-FM) for live-cell imaging.
- Cryo-electron tomography (cryo-ET) for high-resolution structural analysis.
- Investigating the localization and function of MAP6d1 in neuronal primary cilia.
Main Results:
- MAP6d1 facilitates the assembly of stable microtubule doublets by recruiting tubulin dimers to the A-tubule lattice, initiating B-tubule nucleation.
- MAP6d1 promotes the formation of luminal protofilaments in singlet and doublet microtubules, enhancing their stability.
- Loss of MAP6d1 in neurons results in shortened primary cilia, a phenotype associated with ciliopathies.
Conclusions:
- MAP6d1 is a neuronal protein essential for the proper assembly of microtubule doublets in cilia.
- MAP6d1's function in regulating microtubule stability and ciliary length is critical and linked to ciliopathies.
- The discovery of MAP6d1's role in microtubule lumenal protofilament formation offers new insights into microtubule structural regulation.
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