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| Open AccessUncovering structural themes across cilia microtubule inner proteins with implications for human cilia function
The inside surface of microtubules contains so-called microtubule inner proteins, but little is known about their identity. Here the authors use bioinformatics to identify structural motifs within this class of proteins and potential new members.
- Jens S. Andersen
- , Aaran Vijayakumaran
- & Kenneth Bødtker Schou
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Article
| Open AccessMolecular basis promoting centriole triplet microtubule assembly
Centrioles are characterized by an atypical triplet microtubule structure. Here, the authors discover that the ciliopathy protein HYLS1 promotes the assembly of triplet microtubules within human centrioles.
- Yutaka Takeda
- , Takumi Chinen
- & Daiju Kitagawa
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Article
| Open AccessFocal adhesions contain three specialized actin nanoscale layers
Focal adhesions are dynamic structures that link the cell to the extracellular matrix. Here, the authors report that focal adhesions contain tropomyosin-decorated actin filaments, and show evidence that suggests specific functions in adhesion dynamics and cell migration.
- Reena Kumari
- , Katharina Ven
- & Pekka Lappalainen
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Article
| 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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Article
| Open AccessCytokinetic abscission requires actin-dependent microtubule severing
Completion of cell division requires severing both the microtubules and the plasma membrane that connects daughter cells. Here, the authors show that branched actin regulates ESCRT localization to promote the microtubule cut, which happens before membrane scission.
- Tamara Advedissian
- , Stéphane Frémont
- & Arnaud Echard
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Article
| Open AccessQuantitative live cell imaging of a tauopathy model enables the identification of a polypharmacological drug candidate that restores physiological microtubule interaction
In tauopathies, the microtubule-associated protein tau is hyperphosphorylated and aggregated. Here the authors identified a polypharmacological small molecule that inhibits aggregation, reduces phosphorylation, and restores microtubule interaction of tau.
- Luca Pinzi
- , Christian Conze
- & Roland Brandt
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Article
| Open AccessSustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins
The authors identified a series of cytoskeletal proteins involved in the discharge of invasion-related organelles in Toxoplasma gondii. They successfully delineated their functions through the utilization of expansion and cryo-electron microscopy.
- Nicolas Dos Santos Pacheco
- , Albert Tell i Puig
- & Dominique Soldati-Favre
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Article
| Open AccessSTYXL1 regulates CCT complex assembly and flagellar tubulin folding in sperm formation
The sperm flagellum is composed of tubulin-based microtubules and is critical for sperm motility and thus male fertility. Here, the authors show that STYXL1 regulates CCT complex-facilitated tubulin folding and is essential for sperm flagella formation.
- Yu Chen
- , Mengjiao Luo
- & Xuejiang Guo
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Article
| Open AccessVesicles driven by dynein and kinesin exhibit directional reversals without regulators
Intracellular transport along microtubules involves runs, pauses and directional reversals. Here, D’Souza et al. mimic these dynamics in vitro using a minimal system of Dynein-Dynactin-BICD2 and Kinesin-3 on vesicles without the need for regulators.
- Ashwin I. D’Souza
- , Rahul Grover
- & Stefan Diez
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Article
| Open AccessConfined-microtubule assembly shapes three-dimensional cell wall structures in xylem vessels
In plant metaxylem, three-dimensional cell wall arches are formed over pit membranes. Here, the authors show that the microtubule-associated proteins, MAP70-5 and MAP70-1, confine microtubules within the pit aperture and direct growth of pit arches in the proper orientation.
- Takema Sasaki
- , Kei Saito
- & Yoshihisa Oda
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Article
| Open AccessPolarized microtubule remodeling transforms the morphology of reactive microglia and drives cytokine release
Microglia drastically change their morphology when reacting to pathological stimuli. Here, the authors study the molecular responses to stimulation and unravel cytoskeleton remodeling pathways that induce morphological and functional changes.
- Max Adrian
- , Martin Weber
- & Casper C. Hoogenraad
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Article
| Open AccessFAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction
Microtubule inner proteins (MIPs) contribute to species-specific motility characteristics but are largely unstudied. Here, the authors combine functional, structural and proteomic analysis in T. brucei to advance fundamental understanding of MIP assembly and identify trypanosome-specific MIPs required for motility.
- Michelle M. Shimogawa
- , Angeline S. Wijono
- & Kent L. Hill
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Article
| Open AccessControl of motor landing and processivity by the CAP-Gly domain in the KIF13B tail
Intracellular transport of material along microtubules by kinesin motors is critical for cellular homeostasis. Here the authors uncover a unique role for a specialized kinesin tail domain in directing motor transport along specific microtubule tracks.
- Xiangyu Fan
- & Richard J. McKenney
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Article
| Open AccessAcentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract
Microtubules need to be generated during cell division to build mitotic or meiotic spindles. Here, reconstitution experiments and theoretical modeling show that chromosomes alone can trigger branching microtubule nucleation.
- Bernardo Gouveia
- , Sagar U. Setru
- & Sabine Petry
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Article
| Open AccessApicobasal RNA asymmetries regulate cell fate in the early mouse embryo
How do cells of the preimplantation mouse embryo make decisions? Here the authors discovered that the spatial sorting of mRNAs, tRNA, rRNAs and organelles lead to localized translation, conducive for cell fate allocation and embryonic development.
- Azelle Hawdon
- , Niall D. Geoghegan
- & Jennifer Zenker
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Article
| Open AccessEB1 decoration of microtubule lattice facilitates spindle-kinetochore lateral attachment in Plasmodium male gametogenesis
EB are conserved microtubule (MT) plus-end binding proteins. Here, Yang et al. report that Plasmodium EB1 possesses distinct MT-lattice affinity and decorates the full-length of spindle MTs. Gene deletion impairs the spindle-kinetochore lateral attachment, leading to anucleated male gametes.
- Shuzhen Yang
- , Mengya Cai
- & Jing Yuan
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Comment
| Open AccessStructural insights into how augmin augments the mitotic spindle
Cell division critically requires amplification of microtubules (MTs) in the bipolar mitotic spindle. This relies on the filamentous augmin complex that enables MT branching. Studies by Gabel et al., Zupa et al. and Travis et al. describe consistent integrated atomic models of the extraordinarily flexible augmin complex. Their work prompts the question: what is this flexibility really needed for?
- Szymon W. Manka
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Article
| Open AccessIntegrated model of the vertebrate augmin complex
Many microtubules in the mitotic spindle are made through microtubule branching. Here, the authors report a structural model of the augmin complex and insights into its role in microtubule branching.
- Sophie M. Travis
- , Brian P. Mahon
- & Sabine Petry
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Article
| Open AccessTRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport
The mechanisms of microtubule-based mitochondrial transport remain poorly understood. Here, the authors show that the mitochondrial TRAK adaptors activate the dynein-dynactin complex, enhance the motility of kinesin, and can scaffold both motors to control bidirectional transport.
- John T. Canty
- , Andrew Hensley
- & Ahmet Yildiz
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Article
| Open AccessVariable microtubule architecture in the malaria parasite
Microtubules are a ubiquitous eukaryotic cytoskeletal element typically consisting of 13 protofilaments arranged in a hollow cylinder. Using CryoEM and subvolume averaging, Ferreira and Pražák et al. show that Plasmodium does not adhere to a single microtubule structure. Instead, the cytoskeleton changes substantially to produce a unique, fit for purpose structure and organisation at each stage of its life cycle.
- Josie L. Ferreira
- , Vojtěch Pražák
- & Kay Grünewald
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Article
| Open AccessMicrotubule nucleation and γTuRC centrosome localization in interphase cells require ch-TOG
The molecular mechanisms underpinning the organization of microtubule arrays remain unclear. Here the authors show that in human cells, the microtubule polymerase ch-TOG promotes nucleation of microtubules at the interphase centrosome and the Golgi through a mechanism that involves transient interaction with the microtubule nucleator γTuRC.
- Aamir Ali
- , Chithran Vineethakumari
- & Jens Lüders
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Article
| Open AccessActin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations
Lamin A/C gene mutations cause dilated cardiomyopathy associated with cofilin-1 phosphorylation and actin destabilization. Here, the authors show that phosphorylated cofilin-1 blunts the MRTF-A/SRF axis, leading to decreased tubulin acetylation and altered cardiac structure and function.
- Caroline Le Dour
- , Maria Chatzifrangkeskou
- & Antoine Muchir
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Article
| Open AccessKinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
Mitotic spindle assembly is not fully understood. This work reveals that kinetochores drive the coarsening of a uniform microtubule array into bundles, which promote spindle formation and chromosome segregation fidelity.
- Jurica Matković
- , Subhadip Ghosh
- & Iva M. Tolić
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Article
| Open AccessActin polymerization promotes invagination of flat clathrin-coated lattices in mammalian cells by pushing at lattice edges
The role of actin filaments in clathrin-mediated endocytosis (CME) is unclear. Here, Yang et al. show that branched actin filaments promote CME by pushing on clathrin coat edges in an epsin-dependent manner, dividing large flat clathrin plaques into sizes that facilitate invagination.
- Changsong Yang
- , Patricia Colosi
- & Tatyana Svitkina
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Article
| Open AccessThe augmin complex architecture reveals structural insights into microtubule branching
The formation of branched microtubule networks in mitotic spindles depends on the augmin complex. Zupa, Würtz et al. elucidate the molecular architecture and conformational plasticity of the augmin complex using integrative structural biology, providing structural insights into microtubule branching.
- Erik Zupa
- , Martin Würtz
- & Stefan Pfeffer
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Article
| Open AccessMolecular architecture of the augmin complex
The eight-subunit augmin complex is required to nucleate branching microtubules and create a robust mitotic spindle during cell division. Here, the authors use cryo-EM, crosslinking mass spectrometry, and computational tools to build a structural model of the human augmin complex.
- Clinton A. Gabel
- , Zhuang Li
- & Leifu Chang
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Article
| Open AccessEvidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules
Microtubules are built from GDP-tubulin lattices with small GTP caps at their plus-ends. Here, the authors reveal that microtubules that attach to kinetochores in mitosis contain, in addition to the GTP-cap and the GDP-lattices, a dynamic micron-sized mixed-nucleotide zone.
- Cédric Castrogiovanni
- , Alessio V. Inchingolo
- & Patrick Meraldi
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Article
| Open AccessSynaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis
How pancreatic islets of Langerhans are built during development is incompletely understood. Here the authors find that Synaptotagmin-13 mediates remodeling of cell-matrix adhesion to regulate endocrine cell egression and islet morphogenesis.
- Mostafa Bakhti
- , Aimée Bastidas-Ponce
- & Heiko Lickert
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Article
| Open AccessMicrotubule disassembly by caspases is an important rate-limiting step of cell extrusion
Using the Drosophila pupal notum, the authors demonstrate that the disassembly of microtubules by effector caspases initiate cell extrusion independently of actomyosin regulation, thus providing insights into how caspases orchestrate dying epithelial cell expulsion.
- Alexis Villars
- , Alexis Matamoro-Vidal
- & Romain Levayer
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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 AccessRecruitment of two Ndc80 complexes via the CENP-T pathway is sufficient for kinetochore functions
The kinetochores contain multiple protein interaction networks. Takenoshita et al. analyzed the complicated networks using the genetic method and revealed that two copies of Ndc80 complexes on CENP-T are sufficient for kinetochore functions.
- Yusuke Takenoshita
- , Masatoshi Hara
- & Tatsuo Fukagawa
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Article
| Open AccessModular assembly of the principal microtubule nucleator γ-TuRC
The human microtubule nucleator γ-TuRC is composed of more than thirty subunits, including actin. Here the authors reveal the structural mechanism of modular γ-TuRC assembly and show a functional role of actin in microtubule nucleation.
- Martin Würtz
- , Erik Zupa
- & Stefan Pfeffer
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Article
| Open AccessNuMA regulates mitotic spindle assembly, structural dynamics and function via phase separation
Mitotic spindle assembly is required for proper cell division, but many underlying mechanisms remain unclear. Here, the authors show that NuMa undergoes liquid-liquid phase separation, condensing on spindle poles during mitotic entry and enriching critical components to promote spindle assembly.
- Mengjie Sun
- , Mingkang Jia
- & Chuanmao Zhang
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Article
| Open AccessMicrotubule-based transport is essential to distribute RNA and nascent protein in skeletal muscle
It is increasingly recognised that the spatial localisation of RNA is important for proper cellular function. Here, the authors investigate RNA localisation in skeletal muscle and develop methods to show that global active transport of RNA is required to maintain dispersion of gene products in the large muscle syncytium.
- Lance T. Denes
- , Chase P. Kelley
- & Eric T. Wang
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Article
| Open AccessSub-centrosomal mapping identifies augmin-γTuRC as part of a centriole-stabilizing scaffold
The γ-tubulin ring complex (γTuRC) nucleates microtubules at the centrosome, but how this function is related to γTuRC subcentrosomal distribution is unclear. Here the authors show that γTuRC in the centriole lumen has a nucleation-independent role in centriole integrity and cilium assembly.
- Nina Schweizer
- , Laurence Haren
- & Jens Lüders
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Article
| Open AccessWdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules
Ciliary beating is mediated by the axonemal central pair microtubules, though how these non-centrosomal microtubules form is poorly understood. Here the authors show that a trio of proteins act cooperatively to initiate central microtubule formation in mammals.
- Hao Liu
- , Jianqun Zheng
- & Xiumin Yan
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Article
| Open Accessα-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation
Post-translational modifications of tubulins regulate microtubule properties and neural development. Here, the authors report that one such post-translational modification, α-TubK40me3, is required for neuronal polarization and migration by promoting microtubule formation.
- Xuan Xie
- , Shaogang Wang
- & Lan Bao
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Article
| Open AccessAn anchoring complex recruits katanin for microtubule severing at the plant cortical nucleation sites
Katanin severs microtubules to facilitate array reorientation and amplification. Here the authors show that a conserved centrosomal complex of Msd1 and Wdr8 recruits katanin to cortical nucleation sites in acentrosomal plant cells and stabilizes daughter microtubules until they are severed by katanin.
- Noriyoshi Yagi
- , Takehide Kato
- & Takashi Hashimoto
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Article
| Open AccessCryo-EM structure of cortical microtubules from human parasite Toxoplasma gondii identifies their microtubule inner proteins
Cortical microtubules (MTs) in Apicomplexa are specialized MTs involved in maintaining the parasite’s shape and are, as such, unusually stable. Here, cryo-EM analysis of cortical MTs from Toxoplasma gondii offers insight into the mechanism of their stabilization by three bona fide microtubule inner proteins.
- Xiangli Wang
- , Yong Fu
- & Rui Zhang
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Article
| Open AccessIron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia
Debilitating anemias in chronic diseases can result from deficient iron delivery to red cell precursors. Here, the authors show how this deficiency damages the cytoskeletal framework of progenitor cells and identify a targeted strategy for cytoskeletal repair, leading to anemia correction.
- Adam N. Goldfarb
- , Katie C. Freeman
- & Lorrie L. Delehanty
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Article
| Open AccessMicrotubules orchestrate local translation to enable cardiac growth
New contractile units are required during cardiac hypertrophy, though it remains unclear precisely where and how these new sarcomeres are added. Here the authors reveal that in the heart, microtubules spatiotemporally regulate mRNAs and ribosomes to build new sarcomeres, a role which is essential for growth.
- Emily A. Scarborough
- , Keita Uchida
- & Benjamin L. Prosser
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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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Article
| Open AccessThe cryo-EM structure of a γ-TuSC elucidates architecture and regulation of minimal microtubule nucleation systems
The nucleation of microtubules from αβ-tubulin subunits is mediated by γtubulin complexes, which vary in composition across organisms. Here, authors present the cryo-EM structure of the heterotetrameric γ-tubulin small complex (γ-TuSC) from C. albicans at near-atomic resolution.
- Erik Zupa
- , Anjun Zheng
- & Stefan Pfeffer
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Article
| Open AccessPhotoswitchable paclitaxel-based microtubule stabilisers allow optical control over the microtubule cytoskeleton
Light-based modulation of the microtubule (MT) cytoskeleton is an attractive goal for spatiotemporally-resolved MT studies. Here the authors develop a first generation photoswitchable small molecule MT stabiliser based on paclitaxel, allowing optical control over cellular MT dynamics.
- Adrian Müller-Deku
- , Joyce C. M. Meiring
- & Oliver Thorn-Seshold
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Article
| Open AccessIn vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells
The regulation of microtubule (MT) dynamics in cancer cells within the tumor microenvironment is less understood. Here, the authors develop an imaging platform to examine MT dynamics in live xenograft models and show that pro-tumor macrophages modulate MT coherence and alignment to promote cancer cell migration.
- Gaurav Luthria
- , Ran Li
- & Miles A. Miller
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Article
| Open AccessPhase separation of TPX2 enhances and spatially coordinates microtubule nucleation
The microtubule binding protein TPX2 enhances branching microtubule nucleation though the current mechanisms are unclear. Here, the authors show that TPX2 undergoes liquid-liquid phase separation and co-condensates with tubulin to enhance TPX2-mediated microtubule nucleation.
- Matthew R. King
- & Sabine Petry
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Article
| Open AccessActin-microtubule interplay coordinates spindle assembly in human oocytes
Actin and microtubules contribute to successful oocyte maturation, but if and how these two networks communicate in human oocytes is unclear. Here the authors show that actin-microtubule interactions are essential for correct segregation of human nuclear genomic content.
- Johannes Roeles
- & Georgios Tsiavaliaris
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Perspective
| Open AccessAre microtubules tension sensors?
Cellular mechanical stress is a key determinant of cell shape and function, but how the cell senses stress direction is unclear. In this Perspective the authors propose that microtubules autonomously sense stress directions in plant cells, where tensile stresses are higher than in animal cells.
- Olivier Hamant
- , Daisuke Inoue
- & Eric Mjolsness
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Article
| Open AccessThe dynamic and structural properties of axonemal tubulins support the high length stability of cilia
The axoneme in cilia and flagella has exceptionally high stability despite being composed of microtubules that are known to be highly dynamic. Here authors extract tubulin from different components of Chlamydomonas reinhardtii axonemes and characterize their properties.
- Ron Orbach
- & Jonathon Howard