Myo19 tethers mitochondria to endoplasmic reticulum-associated actin to promote mitochondrial fission

Mitochondrial homeostasis requires a dynamic balance of fission and fusion. The actin cytoskeleton promotes fission, and we found that the mitochondrially localized myosin, myosin 19 (Myo19), is integral to this process. Myo19 knockdown induced mitochondrial elongation, whereas Myo19 overexpression induced fragmentation. This mitochondrial fragmentation was blocked by a Myo19 mutation predicted to inhibit ATPase activity and strong actin binding but not by mutations predicted to affect the working stroke of the motor that preserve ATPase activity. Super-resolution imaging indicated a dispersed localization of Myo19 on mitochondria, which we found to be dependent on metaxins. These observations suggest that Myo19 acts as a dynamic actin-binding tether that facilitates mitochondrial fragmentation. Myo19-driven fragmentation was blocked by depletion of either the CAAX splice variant of the endoplasmic reticulum (ER)- anchored formin INF2 or the mitochondrially localized F-actin nucleator Spire1C (a splice variant of Spire1), which together polymerize actin at sites of mitochondria–ER contact for fission. These observations imply that Myo19 promotes fission by stabilizing mitochondria–ER contacts; we used a split-luciferase system to demonstrate a reduction in these contacts following Myo19 depletion. Our data support a model in which Myo19 tethers mitochondria to ER- associated actin to promote mitochondrial fission

MAP1B Regulates Axonal Development by Modulating Rho-GTPase Rac1 Activity

This article shows a novel function for the MAP1B protein, related to the control of actin dynamics through interaction with Tiam1

A reference human induced pluripotent stem cell line for large-scale collaborative studies

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field

Transcription Factor NF-κB Is Transported to the Nucleus via Cytoplasmic Dynein/Dynactin Motor Complex in Hippocampal Neurons

Mikenberg I, Widera D, Kaus A, Kaltschmidt B, Kaltschmidt C. Transcription Factor NF-kappa B Is Transported to the Nucleus via Cytoplasmic Dynein/Dynactin Motor Complex in Hippocampal Neurons. PLOS ONE. 2007;2(7):e589.Background. Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-kappa B. Transcription factors of the NF-kappa B family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. Principal Findings. In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-kappa B to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-kappa B p65 and reduces NF-kappa B-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-kappa B p65 is essential for this binding. Conclusion. This study shows the molecular mechanism for the retrograde transport of activated NF-kappa B from distant synaptic sites towards the nucleus

Strategic directions in constraint programming

An abstract is not available

Dysfunction of Heterotrimeric Kinesin-2 in Rod Photoreceptor Cells and the Role of Opsin Mislocalization in Rapid Cell Death

Loss of kinesin-2 function causes rapid death of rod photoreceptors. The cell death is dependent on the expression of opsin, which first accumulates along the route to the outer segment, but not on signaling by opsin-arrestin complexes or by light activation; the key element appears to be the accumulation of excessive protein in the wrong place