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| Open AccessMicrotubule damage shapes the acetylation gradient
Microtubules are acetylated on the inside of their hollow lumen, a modification linked to their lifespan. Here, the authors show that damage holes act as entry points for a deacetylase to access the lumen, thereby locally counteracting acetylation.
- Mireia Andreu-Carbó
- , Cornelia Egoldt
- & Charlotte Aumeier
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| Open AccessAutoinhibition and activation of myosin VI revealed by its cryo-EM structure
This study reveals the high-resolution cryo-EM structure of autoinhibited myosin VI, offering insights into cargo-mediated activation of this unique myosin motor and advancing our understanding of motor activity control in the myosin superfamily.
- Fengfeng Niu
- , Lingxuan Li
- & Zhiyi Wei
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Article
| Open AccessNde1 promotes Lis1-mediated activation of dynein
Lis1 and Nde1/Ndel1 mediate the initiation of dynein-driven transport, but the mechanism remains unclear. Here, the authors reveal that Nde1 recruits Lis1 to autoinhibited dynein and promotes Lis1-mediated assembly of active dynein transport machinery.
- Yuanchang Zhao
- , Sena Oten
- & Ahmet Yildiz
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| Open AccessBidirectional lysosome transport: a balancing act between ARL8 effectors
Most organelles move bidirectionally on microtubule tracks, yet how this opposing movement is regulated by kinesin and dynein remains unclear. Recent work found that ARL8, a known anterograde adaptor linking the lysosome to kinesin, also links lysosomes to the retrograde motor dynein, providing key insight into bidirectional organelle movement in cells.
- Agnieszka A. Kendrick
- & Jenna R. Christensen
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| Open AccessThe architecture of kinesin-3 KLP-6 reveals a multilevel-lockdown mechanism for autoinhibition
Autoinhibition ensures the proper spatiotemporal control of the kinesin-3 motor activity. Here, the authors present the full-length structure of kinesin-3 KLP-6 in an autoinhibited state and observe that all the internal domains entwine around the motor domain via a multilevel-lockdown mechanism.
- Wenjuan Wang
- , Jinqi Ren
- & Wei Feng
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Article
| Open AccessThe force required to remove tubulin from the microtubule lattice by pulling on its α-tubulin C-terminal tail
Tubulin, the building blocks of microtubules, can be removed from the microtubule wall by mechanical forces. Using single-molecule methods, the authors show that tubulin partially unfolds prior to its removal and determined the tubulin-extraction force.
- Yin-Wei Kuo
- , Mohammed Mahamdeh
- & Jonathon Howard
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Article
| Open AccessMetaxins are core components of mitochondrial transport adaptor complexes
Mitochondrial trafficking is carefully regulated and functionally important in neurons. Here, the authors screen C. elegans for abnormal mitochondrial distribution and identify metaxin-1 and -2, which bind Miro and microtubule motor proteins to promote mitochondrial trafficking.
- Yinsuo Zhao
- , Eli Song
- & Kang Shen
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| Open AccessMiro clusters regulate ER-mitochondria contact sites and link cristae organization to the mitochondrial transport machinery
Mitochondrial cristae organization and ER-mitochondria contact sites are critical structures for cellular function. Here, the authors use super-resolution microscopy to show that Miro GTPases form clusters required for normal ER-mitochondria contact sites formation and to link cristae organization to the mitochondrial transport machinery.
- Souvik Modi
- , Guillermo López-Doménech
- & Josef T. Kittler
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| Open AccessReconstitution reveals how myosin-VI self-organises to generate a dynamic mechanism of membrane sculpting
Curvature-mediating proteins are known to induce specific membrane shapes, but whether motorprotein-lipid interactions remodel membranes too remains unclear. Here authors show that curvature-dependent lipid interactions of myosin-VI remodel the membrane geometry into dynamic spatial patterns.
- Benoit Rogez
- , Laeschkir Würthner
- & Claudia Veigel
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| Open AccessPTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport
The kinesin-3 KIF1C transports dense core vesicles in neurons and delivers integrins to cell adhesions sites. Here the authors show that KIF1C's autoinhibitory interactions are released upon binding of protein tyrosine phosphatase PTPN21 or cargo adapter Hook3 resulting in cargo-activated transport.
- Nida Siddiqui
- , Alexander James Zwetsloot
- & Anne Straube
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Article
| Open AccessMicrotubule minus-end aster organization is driven by processive HSET-tubulin clusters
Microtubules (MT) form higher-order structures such as asters, but the molecular pathway underlying aster formation remains unclear. Here authors demonstrate that the kinesin-14, HSET, clusters with soluble (nonMT) tubulin via its N-terminal tail domain and thereby promotes MT aster formation.
- Stephen R. Norris
- , Seungyeon Jung
- & Ryoma Ohi
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Article
| Open AccessCryo-EM reveals the structural basis of microtubule depolymerization by kinesin-13s
Kinesin-13s are microtubule depolymerases that lack motile activity. Here the authors present the cryo-EM structures of kinesin-13 microtubule complexes in different nucleotide bound states, which reveal how ATP hydrolysis is linked to conformational changes and propose a model for kinesin induced depolymerisation.
- Matthieu P.M.H. Benoit
- , Ana B. Asenjo
- & Hernando Sosa
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| Open AccessIFT proteins spatially control the geometry of cleavage furrow ingression and lumen positioning
Cytokinesis relies on central spindle organization and provides a spatial landmark for lumen formation. Here, the authors show that intraflagellar transport proteins are required for the localization of the cytokinetic regulator Aurora B and subsequent cleavage furrow ingression and lumen positioning.
- Nicolas Taulet
- , Benjamin Vitre
- & Benedicte Delaval
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Article
| Open AccessOptogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres
Cellular contractility is regulated by the GTPase RhoA, but how local signals are translated to a cell-level response is not known. Here the authors show that targeted RhoA activation results in propagation of force along stress fibres and actin flow, and identify zyxin as a regulator of stress fibre mechanics and homeostasis.
- Patrick W. Oakes
- , Elizabeth Wagner
- & Margaret L. Gardel
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| Open AccessTwo pathways regulate cortical granule translocation to prevent polyspermy in mouse oocytes
Mammalian eggs release cortical granules to avoid being fertilized by more than a single sperm as polyspermy results in nonviable embryos. Here, the authors describe the mechanism driving translocation of the granules to the cortex in the mouse egg and show this process is essential to prevent polyspermy.
- Liam P. Cheeseman
- , Jérôme Boulanger
- & Melina Schuh
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| Open AccessEngineered kinesin motor proteins amenable to small-molecule inhibition
The use of specific small molecule inhibitors can contribute to the study of kinesins' cellular functions. Here the authors develop a chemical-genetic approach to engineer kinesin motors that can be efficiently inhibited upon addition of cell-permeable molecules.
- Martin F. Engelke
- , Michael Winding
- & Kristen J. Verhey
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| Open AccessKinesin-5 is a microtubule polymerase
Kinesin-5 is a tetrameric motor that slides antiparallel microtubules during mitotic spindle assembly. Chen and Hancock show that this motor also promotes microtubule assembly by stabilising protofilaments at growing plus ends, which results in the formation of banana peel-like structures.
- Yalei Chen
- & William O Hancock
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| Open AccessDirect observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules
Cytoplasmic dynein is a dimeric protein that steps processively along microtubules. Here Imaiet al. present cryo-electron microscopy images of stepping D. discoideumdynein, revealing diverse microtubule-bound configurations including a hinge-dependent, motors side-by-side arrangement.
- Hiroshi Imai
- , Tomohiro Shima
- & Stan A. Burgess
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HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus
Many viruses take advantage of microtubule-dependent motor proteins to move through the cell. Malikov et al. show that HIV-1 recruits the kinesin-1 adaptor FEZ1, and that the opposing activities of kinesin-1 and dynein motors are both required for the transport of HIV-1 capsids towards the nucleus.
- Viacheslav Malikov
- , Eveline Santos da Silva
- & Mojgan H. Naghavi
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Arl3 and LC8 regulate dissociation of dynactin from dynein
Cargo is transported through the cell on microtubules, but the regulatory mechanism controlling release of dynactin-bound cargo from dynein is not known. Here, Jin et al.uncover roles for ADP-ribosylation factor-like 3 (Arl3) and dynein light chain LC8 in unloading cargo from microtubules.
- Mingyue Jin
- , Masami Yamada
- & Shinji Hirotsune