The manchette is a transient microtubule (MT)-based structure that is vital for the correct shaping of sperm during spermiogenesis. Throughout spermiogenesis, the manchette retains structural integrity for several days, raising the question of how its MTs are regulated. Here, using cryo-electron tomography of manchettes isolated from rat testes, we find that manchette MT ends are structurally diverse. We show that the MT-binding protein CLASP2 is present throughout the manchette and likely regulates both MT ends. Using cryo-electron microscopy single particle analysis and super-resolution microscopy, we reveal that SPACA9 and MNMIP1 (SH3D21) bind to the seam of manchette MTs from the luminal side. SPACA9 binds to both α- and β-tubulin of protofilament 1 but does not interact directly with protofilament 13, while MNMIP1 binds directly to protofilament 13. MNMIP1 further extends and threads through the MT lattice at the seam. Our study reveals a novel seam MT inner protein complex with a unique binding mode, providing a plausible explanation for MT regulation that maintains manchette integrity over an extended period.

Nature Reviews Molecular Cell Biology, Published online: 27 November 2025; doi:10.1038/s41580-025-00921-5The centriole is crucial for fundamental cellular processes in eukaryotes, including cell polarity, signalling and motility. This Review discusses recent insights into the molecular architecture of centrioles and the principles governing their assembly, with a focus on human cells.

imageimageDynein-2 is a motor protein essential for retrograde intraflagellar transport (IFT) on the A-tubule of ciliary doublet microtubules. Here, biochemical and cryo-ET analyses demonstrate that d...

Journal of Cell Science publishes cutting-edge science encompassing all aspects of cell biology. It is published by The Company of Biologists, a not-for-profit organisation.

Summary: This Review explores proteomic strategies for investigating cilia, tracing the evolution from early discoveries to recent advancements enabled by proximity labeling techniques.

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Summary: Microtubule inner proteins (MIPs) have been brought into focus by the cryo-EM revolution. This Review outlines current knowledge, emerging functions, links to ciliopathies and outstanding que...

Nature Structural & Molecular Biology, Published online: 29 September 2025; doi:10.1038/s41594-025-01680-9Issa et al. show that the ciliary small guanosine triphosphatase Arl3 displaces the inhibitory regulator Shulin/DNAAF9 from the outer dynein arm, leading to motor activation.

Linker of nucleo- and cytoskeleton (LINC) complexes reside in the nuclear envelope, the double-membrane surrounding the nucleus, where they establish a physical bridge between nucleus and cytoplasm. L...

Cryo-electron microscopy and biochemical reconstitution analysis reveals that Nde1 enhances Lis1 binding to autoinhibited dynein, promoting formation of a Phi-like–Lis1 intermediate during dynein acti...

Job Title: Associate or Senior Editor, Nature Biomedical Engineering Organization: Nature Portfolio Location: New York, Jersey City, Shanghai or Beijing – Hybrid Working Closing date: August 20, 2025 ...

Title: Associate or Senior Editor, Nature Methods Organization: Nature Portfolio Locations: New York, Jersey City, Shanghai or Beijing Closing Date: August 3, 2025    About Springer Nature Springer Na...

Cell generate forces to maintain normal tissue morphology and function. Cells can also sense and process forces appropriate to their correct tissue context. ...

During mitosis, properly aligned chromosomes stabilise microtubule ends with the help of kinetochores to ensure timely segregation of chromosomes. Microtubule-binding components of the human outer kinetochore, such as Ndc80 and Ska complexes, are present in multiple copies and together bind several microtubule ends, creating a highly multivalent binding interface. Whereas Ndc80:Ndc80 and Ndc80:microtubule binding is crucial for interface stability, Ndc80 alone in absence of Ska is unable to support stable kinetochore-attachments. Using cryoET, we demonstrate that oligomeric Ndc80:Ska assemblies stabilise microtubule ends against shortening by strengthening lateral contacts between tubulin protofilaments at microtubule plus-ends. We further identify a point mutation within the SKA1 microtubule-binding domain that does not affect microtubule-binding of individual Ska molecules, but does abolish Ska:Ska interactions. Finally, we report that oligomerisation of Ska, in a cooperative fashion together with the Ndc80, is necessary to maintain stable microtubule attachments both in vivo and in vitro. ### Competing Interest Statement The authors have declared no competing interest. BBSRC, BB/X014975/1, BB/W019698/1 Wellcome Trust, https://ror.org/029chgv08, 308895/Z/23/Z

Cilia are composed of microtubule doublets, but how they assemble is unclear. Here, the authors show that the brain-specific MAP6d1, found in neuronal primary cilia, assembles doublet microtubules and...

SARS-CoV-2 entry into host cells is mediated by the spike protein, which drives membrane fusion. While cryo-EM reveals stable prefusion and postfusion conformations of the spike, the transient fusion intermediate states during the fusion process remain poorly understood. Here, we design a near-native viral fusion system that recapitulates SARS-CoV-2 entry and use cryo-electron tomography (cryo-ET) to capture fusion intermediates leading to complete fusion. The spike protein undergoes extensive structural rearrangements, progressing through extended, partially folded, and fully folded intermediates prior to fusion-pore formation, a process that depends on protease cleavage and is inhibited by the WS6 S2 antibody. Upon interaction with ACE2 receptor dimer, spikes cluster at membrane interfaces and following S2’ cleavage concurrently transition to postfusion conformations encircling the hemifusion and initial fusion pores in a distinct conical arrangement. S2’ cleavage is indispensable fo

Nature Structural & Molecular Biology, Published online: 23 May 2025; doi:10.1038/s41594-025-01558-wUsing cryo-EM, Kendrick et al. reveal multiple dynein conformations during dynein’s mechanochemical cycle and Lis1 binding that represent intermediate states of dynein’s activation.

Nature Reviews Molecular Cell Biology, Published online: 14 May 2025; doi:10.1038/s41580-025-00854-zThe inner mitochondrial membrane forms cristae, which are crucial for mitochondrial function. This Review explores the protein complexes that regulate cristae dynamics, including remodelling and fusion, and discusses recent structural insights that have increased our understanding of mitochondrial architecture.

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A single taste receptor initiates our reactions to both sugars and artificial sweeteners, triggering a signaling process that drives our intense attraction to sweet foods. Single-particle cryo-EM reve...

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The temporospatial distribution of proteins within cilia is regulated by intraflagellar transport (IFT), wherein molecular trains shuttle between the cell body and cilium. Defects in this process impair various signal-transduction pathways and cause ciliopathies. Although K63-linked ubiquitination appears to trigger protein export from cilia, the mechanisms coupling polyubiquitinated proteins to IFT remain unclear. Using a multidisciplinary approach, we demonstrate that a complex of CFAP36, a conserved ciliary protein of previously unknown function, and ARL3, a GTPase involved in ciliary import, binds polyubiquitinated proteins and links them to retrograde IFT trains. CFAP36 uses a coincidence detection mechanism to simultaneously bind two IFT subunits accessible only in retrograde trains. Depleting CFAP36 accumulates K63-linked ubiquitin in cilia and disrupts Hedgehog signaling, a pathway reliant on the retrieval of ubiquitinated receptors. These findings advance our understanding of ubiquitin-mediated protein transport and ciliary homeostasis, and demonstrate how structural changes in IFT trains achieve cargo selectivity. ### Competing Interest Statement The authors have declared no competing interest. Sara Elizabeth O'Brien Trust Postdoctoral Fellowship awarded through the Charles A. King Trust Postdoctoral Research Fellowship Program, , 8460873-01 Richard and Susan Smith Family Foundation, https://ror.org/05j95n956, National Institute of General Medical Sciences (NIGMS), , R01GM141109, R01GM143183

Goethe University Frankfurt am Main invites applications for the position of Professor (W3) in Organic Synthesis at the Faculty of Biochemistry, Ch...

Nature Structural & Molecular Biology, Published online: 22 April 2025; doi:10.1038/s41594-025-01543-3Chai et al. use cryo-electron microscopy to systematically interrogate the conformational landscape of motor protein dynein. The reported structures reveal intermediate states in the mechanochemical cycle of dynein, the role of adenosine triphosphate and the communication mechanism with microtubules.