Microtubule structural heterogeneity: from intrinsic lattice states to cellular function
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Dr. Matthieu BENOIT
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### Researcher at INSERM

### Institut de Génétique & Développement de Rennes (IGDR)

### UMR 6290 CNRS / UR – ERL Team - U1305 INSERM – RENNES

### Co-director of the TEM2C cryo-electron microscopy platform

### BIOSIT UAR 3480 CNRS – US 18 – UNIVERSITE DE RENNES

### **Abstract**

Microtubules are essential cytoskeletal polymers that organize the eukaryotic cell, drive intracellular transport and contribute to processes ranging from cell division to morphogenesis. Their diverse functions depend on their dynamic properties and interactions with numerous microtubule-associated proteins. Structural heterogeneity is a prominent feature of microtubule systems, and resolving it is essential to identify distinct states and understand their biological functions. I will illustrate this through three complementary examples. First, the identification of alternative C- and D-lattice states reveals an unexpected level of intrinsic microtubule heterogeneity with potential consequences for assembly and dynamics. Second, structures of kinesin-microtubule complexes provide mechanistic insight into motor function and the impact of disease-associated mutations. Finally, cryo-EM analysis of spermatid manchette microtubules provides an example of how structural analysis of native cellular assemblies can reveal higher-order molecular organization. Together, these studies highlight how resolving microtubule heterogeneity across scales can provide insight into biological function.