Journal Club – April 2019

Tubulin Beyond Microtubules, Inhibitable Kinesin-2, and Designer Organelles

Must Reads

Tubulin mRNA Stability Is Sensitive To Change In Microtubule Dynamics Caused By Multiple Physiological And Toxic Cues

Gasic, Boswell, and Mitchison | PLoS Biol. As the molecular building blocks of microtubules, alpha- and beta-tubulin heterodimers are subject to cellular surveillance. Studies in the 1980s uncovered a negative feedback loop wherein unpolymerized tubulin affects the biosynthesis of new tubulin protein; however, the details of when and how a cell senses and responds to soluble tubulin protein levels remain largely unknown. In this study, Gasic, Boswell, and Mitchison ask whether tubulin autoregulation is part of a larger differential gene expression (DGE) program using gene-expression analysis in quiescent cells as well as bioinformatic mining of public data sets. The authors find that tubulin mRNA stability is sensitive to changes in microtubule dynamics in a variety of cellular contexts, and argue that a comprehensive understanding of tubulin autoregulation is critical for the enhancement of microtubule-targeting therapies.

Designer Membraneless Organelles Enable Codon Reassignment Of Selected mRNAs In Eukaryotes

Reinkemeier, Girona, and Lemke  |  Science Compartmentalization is fundamental to cell biology. The local enrichment of key molecular players drives essential chemical reactions and boosts cellular efficiency. Inspired by this concept, Reinkemeier et al. leverage the spatial enrichment of kinesins Kif13A and Kif16B at microtubule plus-ends to engineer a synthetic compartment within mammalian cells dedicated to orthogonal translation. The authors propose that their novel approach combining spatial and phase separation inside living cells unlocks new possibilities in synthetic cell engineering.

Long-Range, Through-Lattice Coupling Improves Predictions Of Microtubule Catastrophe

Kim and Rice |  MBoC.  The transition of microtubule polymers from growth to shrinkage is a hallmark of dynamic instability, yet a detailed mechanistic understanding of microtubule catastrophe remains poorly defined. For example, biochemical models of microtubule catastrophe are unable to recapitulate the weak concentration dependence observed in vitro, while more complex mechanochemical models are difficult to interpret. In the latest issue of MBoC, investigators Kim and Rice explore various models of microtubule catastrophe in order to better understand this phenomenon. The authors consider missing biochemical states and discover that accounting for long-range conformational coupling improves predictions of microtubule catastrophe. Drawing parallels to mechanochemical models that distribute strain throughout the microtubule lattice, this study emphasizes the cooperative effects of neighboring tubulin subunits (even when those neighbors are far away).


Using Chemical Inhibitors To Probe AAA Protein Conformational Dynamics And Cellular Functions

A review of the chemistry and experimental utility of AAA ATPase inhibitors, as well as their potential clinical impact.
Steinman and Kapoor  |  Current Opinion In Chemical Biology


A Method Of Quantifying Centrosomes At The Single-Cell Level In Human Normal and Cancer Tissue
An immunofluorescence microscopy–based method for quantifying centrosomes at a single-cell level in different types of human tissue samples.
Wang et al.  |  MBoC


Unsolved Problems in Cell Biology: Reverse Engineering the Collective Action of Macromolecules
by Tim Mitchison  | The American Society For Cell Biology

Reflections On My Life With Taxol
by Susan Band Horwitz | Cell Press

Keep Your Eyes On The Prize
by Ronald Vale | Cell Press

Conference Watch

Meeting organizers recap highlights of the 2018 ASCB Annual Meeting minisymposia…
Spindle Mechanics And Chromosome Segregation  |  Iva Tolić  and Daniel Gerlich
Motors In Transport And Cytoskeleton Remodeling  | Julie Welburn and Michael Ostap
Cell Cycle, Cell Division, Cell Death  | Amy Maddox and Jan Skotheim

Journal Club Picks

  • KIF18A-deficient cells from nontransformed mammalian systems offer new insight into the importance of chromosome alignment during mitosis.
    Fonseca et al.  |  Reinholdt and Stumpff Labs  |  JCB (spotlight by Orr and Maiato)
  • Kinesins with a single motor domain can work as a team to transport intracellular cargos, but dimeric motors are needed to withstand heavy loads.
    Schimert et al.  |  Verhey Lab  |  PNAS
  • Tubulin recruitment by TOG1 and TOG2 functions separately in microtubule plus-end tracking and polymerization.
    Cook et al.  |  Flor-Parra and Al-Bassam Labs  |  MBoC
  • Kinesin-binding protein (KBP) buffers the activity of multiple mitotic kinesins to promote mitotic fidelity.
    Malaby et al.  |  Ohi and Stumpff Labs  |  JCB
  • Septins sense membrane curvature at surprisingly small length scales.
    Cannon et al.  |  Gladfelter Lab  |  JCB (spotlight by McMurray)
  • A novel positron emission tomography (PET) probe targets and degrades pathogenic tau in patient-derived neurons.
    Silva et al.  |  Gray and Haggarty Labs  | eLife
  • Type I myosins assist actin in deforming membranes independent of their motor activity during clathrin-mediated endocytosis.
    Pedersen and Drubin  |  Drubin Lab  |  JCB
  • Myosin IIA drives membrane bleb retraction during cytokinesis, likely benefiting from its fast turnover at the cortex.
    Taneja and Burnette |  Burnette Lab  |  MBoC
  • A systematic study of kinesin-1 regulation by MAP7 proteins delves into the complex interplay between molecular motors and their tracks.
    Hooikaas et al. |  Akhmanova Lab  | JCB
  • Specific and rapid inhibition of an engineered kinesin-2 motor enables the study of its function in ciliated cells.
    Engelke et al.  |  Verhey Lab  |  Current Biology
  • Liquid-liquid phase separation increases the membrane dwell times of N-WASP and Arp2/3 to promote actin assembly at the plasma membrane.
    Case et al.  |  Rosen Lab  |  Science (perspective by Martin and Mittag)
  • Enhanced processivity of Ena/VASP on fascin bundles reveals regulation of actin assembly factors by actin bundle subtypes.
    Harker et al.  |  Kovar Lab  |  MBoC

Our opinions are our own and do not represent the views or endorsement of the authors cited.

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