Syntaxin-1 is necessary for UNC5/Netrin-1-dependent macropinocytosis and chemorepulsion

Brain connectivity requires correct axonal guidance to drive axons to their appropriate targets. This process is orchestrated by guidance cues that exert attraction or repulsion to developing axons. However, the intricacies of the cellular machinery responsible for the correct response of growth cones are just being unveiled. Netrin-1 is a bifunctional molecule involved in axon pathfinding and cell migration that induces repulsion during postnatal cerebellar development. This process is mediated by Uncoordinated locomotion 5 (UNC5) receptors located on external granule layer (EGL) tracts. Here, we demonstrate that this response is characterized by enhanced membrane internalization through macropinocytosis, but not clathrin-mediated endocytosis. We show that UNC5 receptors form a protein complex with the t-SNARE syntaxin-1 (Stx1). By combining botulinum neurotoxins, a shRNA knock-down strategy and Stx1 knock-out mice, we demonstrate that this SNARE protein is required for Netrin-1-induced macropinocytosis and chemorepulsion, suggesting that Stx1 is crucial in regulating Netrin-1-mediated axonal guidance.

A Chemical Approach to 2D-2D Heterostructures Beyond Van Der Waals: High-Throughput On-Device Covalent Connection of MoS2 and Graphene

<p>The most widespread method for the synthesis of 2D-2D heterostructures is the direct growth of one material on top of the other. Alternatively, one can manually stack flakes of different materials. Both methods are limited to one crystal/device at a time and involve interfacing the 2D materials through van der Waals forces, to the point that all these materials are known as van der Waals heterostructures. Synthetic chemistry is the paradigm of atomic-scale control, yet its toolbox remains unexplored for the construction of 2D-2D heterostructures. Here, we describe how to covalently connect 2H-MoS₂ flakes to several single-layer graphene field-effect transistors simultaneously, and show that the final electronic properties of the MoS₂-graphene heterostructure are dominated by the molecular interface. We use a bifunctional molecule with two chemically orthogonal anchor points, selective for sulphides and carbon-based materials. Our experiments highlight the potential of the chemical approach to build 2D-2D heterostructures beyond van der Waals. </p>

A Chemical Approach to 2D-2D Heterostructures Beyond Van Der Waals: High-Throughput On-Device Covalent Connection of MoS2 and Graphene

<p>The most widespread method for the synthesis of 2D-2D heterostructures is the direct growth of one material on top of the other. Alternatively, one can manually stack flakes of different materials. Both methods are limited to one crystal/device at a time and involve interfacing the 2D materials through van der Waals forces, to the point that all these materials are known as van der Waals heterostructures. Synthetic chemistry is the paradigm of atomic-scale control, yet its toolbox remains unexplored for the construction of 2D-2D heterostructures. Here, we describe how to covalently connect 2H-MoS₂ flakes to several single-layer graphene field-effect transistors simultaneously, and show that the final electronic properties of the MoS₂-graphene heterostructure are dominated by the molecular interface. We use a bifunctional molecule with two chemically orthogonal anchor points, selective for sulphides and carbon-based materials. Our experiments highlight the potential of the chemical approach to build 2D-2D heterostructures beyond van der Waals. </p>

Catalyst design in C–H activation: a case study in the use of binding free energies to rationalise intramolecular directing group selectivity in iridium catalysis

In C–H activation chemistries, the interpretation of the influence of remote directing groups in a bifunctional molecule depends on the in silico method used to inform catalyst design.