People & Ideas
Judith Agudo studies the mechanisms that adult and cancer stem cells use to evade the immune response with the goals of engineering autoimmunity- and allograft-resistant stem cells and improving the response of cancer stem cells to immunotherapy.
Mitochondrial membrane biogenesis: A new pathway for lipid transport mediated by PERK/E-Syt1 complex
Leterme and Michaud preview a study by Sassano et al., which reveals an interaction between PERK and E-Syt1 at ER–mitochondria contact sites that facilitates lipid transport and mitochondrial functions.
Güler and Mostowy discuss articles from the Gladfelter lab and from the Mavrakis lab on how the organization of septins into filaments directs their function in yeast and humans, respectively.
Ramsey and Huang highlight work from Hennlein and colleagues which shows that Plastin 3 promotes F-actin–dependent translocation and recycling of TrkB receptor that sustains BDNF–TrkB signaling in spinal motor neurons.
Jiri Neuzil and colleagues review the processes and mechanisms that underlie horizontal mitochondrial transfer (HMT) and the metabolic consequences of HMT in cells.
Nuclear-enriched protein phosphatase 4 ensures outer kinetochore assembly prior to nuclear dissolution
Rocha et al. show that C. elegans protein phosphatase 4 ensures robust outer kinetochore assembly prior to nuclear envelope breakdown, which is critical for timely and proper engagement of mitotic chromosomes with spindle microtubules.
Berman et al. examine the capping activity of the γ-TuRC. Using in vitro and cellular assays, they characterize how the γ-TuRC's nucleotide-independent capping activity regulates microtubule dynamics and how it contributes to microtubule formation during cell division.
A screen for mutants defective in dynein-mediated early endosome transport identified a kinesin-1 mutation that disrupts kinesin-1 autoinhibition. Kinesin-1 autoinhibition is not needed for driving dynein accumulation at microtubule plus ends, but it affects the initiation of dynein-mediated cargo transport.
Beppler et al. show that therapeutic T cells engineered to express chimeric antigen receptors (CARs) use the same dynamic finger-like projections, called microvilli, that facilitate natural T cell receptor (TCR) antigen scanning, but with hyper-stabilized dynamics following receptor binding.
Meiotic resetting of the cellular Sod1 pool is driven by protein aggregation, degradation, and transient LUTI-mediated repression
Vander Wende et al. show that Superoxide dismutase 1 (Sod1), an antioxidant whose aggregation is associated with Amyotrophic Lateral Sclerosis (ALS), is highly regulated during meiosis. This includes regulation of its synthesis, aggregation, and degradation, allowing cells to refresh their pool of this important protein as rejuvenated gametes are created.
ER–mitochondria contact sites (EMCS) regulate non-vesicular phospholipid transport between these organelles, but the molecular entities involved in lipid translocation remain undefined. Sassano et al. reveal that EMCS-associated PERK recruits the lipid transfer protein E-Syt1 at EMCS facilitating lipid transport to sustain mitochondrial homeostasis and respiration.
Miller et al. identify the tomosyn homolog Sro7 as an allosteric activator of the exocyst resulting in specific biochemical changes to the complex. The outcomes of exocyst activation by Sro7 are distinct and insulated from exocyst activation by Rho/Cdc42 GTPases.
Wethekam and Moore investigate how cells balance levels of α- and β-tubulin to supply αβ-heterodimers. They found that cells produce higher levels of α-tubulin than β-tubulin and require this excess to limit β-tubulin accumulation. β-tubulin accumulation causes microtubule loss and formation of dead-end tubulin assemblies.
A gene duplication of a septin reveals a developmentally regulated filament length control mechanism
Cannon et al. identify a gene duplication event of a septin gene showing that two highly similar but distinct septin proteins generate novel biophysical features of septin polymers that can control their size, shape, and function.
Martins et al. show that all septins associated with actin stress fibers organize as octamer-based filaments that mediate actin-membrane anchoring. Depleting octamers or preventing septins from polymerizing leads to a partial loss of stress fibers and compromised cell mechanics.
Mund and Tschanz et al. reveal the three-dimensional shapes of clathrin coats during endocytosis, which partially preassemble and then bend progressively. They further introduce the novel Cooperative Curvature Model, which accurately describes the changes in shapes and dynamics during endocytic clathrin remodeling.
Hennlein et al. show a novel role of the actin-bundler PLS3 that mediates correct surface translocation of the neurotrophin receptor TrkB and proper "cluster-like" formations of voltage-gated Ca2+ channels as processes that are indispensable for development and functional maintenance of motoneurons.
Neurite pruning, a critical neuronal circuit specification mechanism, often involves neurite abscission by unknown mechanisms. In Drosophila sensory neurons, pruning dendrites first become mechanically fragile, and severing occurs through morphogenetic tissue movements that exert mechanical forces on the destabilized dendrites, thus establishing mechanical force as a mechanism during neurite pruning.
Xue et al. develop a system to visualize and compare focal adhesion formation and dynamics during single-cell migration in animal models versus cell culture systems. They reveal fundamental differences in the regulation of key focal adhesion proteins.
Djannatian et al. show by ultrastructural analysis of mouse optic nerves and in vivo imaging of zebrafish spinal cords that developmental myelination is an error-prone process and microglia contribute to the removal of aberrant structures. This may be an important mechanism to generate properly functioning myelin.
Lleti, Steyer, and Schieber et al. present an integrated software that automates correlative light and volume electron microscopy to perform high-resolution volumetric imaging of multiple cells.
We present a method probing the local membrane environment surrounding membrane proteins in the plasma membrane by linking a solvatochromic dye to the target, and provide evidence for lipid-based sorting. The insulin receptor environment changed upon insulin stimulation revealing dynamic local changes and distance dependence.