Biology subjects

Lescure, A.

Publications and source records attributed to Lescure, A..

4 recordsLinked to original sources

bioRxiv2018

MYO1C facilitates arrival at the Golgi apparatus through stabilization of branched actin

We aim at the identification of myosin motor proteins that control trafficking at the Golgi apparatus. In addition to the known Golgi-associated myosins MYO6, MYO18A and MYH9 (myosin IIA), we identify MYO1C as a novel player at the Golgi. We demonstrate that depletion of MYO1C induces Golgi apparatus fragmentation and decompaction. MYO1C accumulates at dynamic structures around the Golgi apparatus that colocalize with Golgi-associated actin dots. Interestingly, MYO1C depletion leads to loss of cellular F-actin, and Golgi apparatus decompaction is also observed after the inhibition or loss of the Arp2/3 complex. We show that the functional consequences of MYO1C depletion is a delay in the arrival of incoming transport carriers, both from the anterograde and retrograde routes. We propose that MYO1C stabilizes branched actin at the Golgi apparatus that facilitates the arrival of incoming transport at the Golgi.

cell biology↗

bioRxiv2018

The small and large ribosomal subunits depend on each other for stability and accumulation

The 1:1 balance between the numbers of large and small ribosomal subunits can be disturbed by mutations that inhibit the assembly of one of the subunits. We have investigated if the cell has mechanisms to counteract an imbalance of subunits. We show that accumulation of 40S subunits stops after abrogating 60S assembly. In contrast, cessation of the 40S pathways does not prevent 60S accumulation, but does, however, lead to fragmentation of the 25S rRNA in 60S subunits. Even though 40S subunits do not accumulate in the absence of 60S assembly, 40S assembly continues, indicating that excess 40S is degraded after assembly. Thus, the cell expends substantial resources in a futile attempt to increase the number of functional 80S ribosomes. We propose that a mechanism for preventing the accumulation of 40S subunits in excess over 60S subunits may have evolved to prevent mRNAs from being tied up in 40S-mRNA translation initiation complexes that cannot be turned into productive translation complexes because of the deficit of 60S subunits.

molecular biology↗

bioRxiv2018

Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs

Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present a hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor and 13 subclonal lines across nine time points over 5 broad conditions: self-renewal, early neuronal differentiation, neural precursor cells (NPCs), assembled rosettes, and differentiated neuronal cells that were validated using electrophysiology. We identified widespread changes in the expression of individual transcript features and their splice variants, gene networks, and global patterns of transcription. We next demonstrated that co-culturing human NPCs with rodent astrocytes resulted in mutually synergistic maturation, and that cell type-specific expression data can be extracted using only sequencing read alignments without potentially disruptive cell sorting. We lastly developed and validated a computational tool to estimate the relative neuronal maturity of iPSC-derived neuronal cultures and human brain tissue, which were maturationally heterogeneous but contained subsets of cells most akin to adult human neurons.

genomics↗

bioRxiv2018

Differential screening identifies molecules specifically inhibiting CCR5 transport to the cell surface and HIV infection

Proteins destined to the cell surface are conveyed through membrane-bound compartments using the secretory pathway. Multiple secretory routes exist in cells, which paves the way to the development of inhibitory molecules able to specifically perturb the transport of a chosen cargo. We used differential high-content screening of chemical libraries to identify molecules reducing the secretion of CCR5, the major co-receptor for HIV-1 entry. Three molecules strongly affected the anterograde transport of CCR5, without inhibiting the transport of the related G protein-coupled receptors CCR1 and CXCR4. These three molecules perturb the transport of endogenous CCR5 and decrease the entry of HIV in human primary target cells. Two molecules were found to share the same mode of action, inhibiting palmitoylation of CCR5. Our results demonstrate that secretory routes can be specifically targeted which allows to envisage novel strategies to provoke the intracellular retention or rerouting of secretory proteins involved in disease development.

cell biology↗