Injured Axons Instruct Schwann Cells to Build Constricting Actin Spheres to Accelerate Axonal Disintegration
Summary: After a peripheral nerve lesion, distal ends of injured axons disintegrate into small fragments that are subsequently cleared by Schwann cells and later by macrophages. Axonal debris clearing is an early step of the repair process that facilitates regeneration. We show here that Schwann cells promote distal cut axon disintegration for timely clearing. By combining cell-based and in vivo models of nerve lesion with mouse genetics, we show that this mechanism is induced by distal cut axons, which signal to Schwann cells through PlGF mediating the activation and upregulation of VEGFR1 in Schwann cells. In turn, VEGFR1 activates Pak1, leading to the formation of constricting actomyosin…
Functions of histone modifications and histone modifiers in Schwann cells.
Schwann cells (SCs) are the main glial cells present in the peripheral nervous system (PNS). Their primary functions are to insulate peripheral axons to protect them from the environment and to enable fast conduction of electric signals along big caliber axons by enwrapping them in a thick myelin sheath rich in lipids. In addition, SCs have the peculiar ability to foster axonal regrowth after a lesion by demyelinating and converting into repair cells that secrete neurotrophic factors and guide axons back to their former target to finally remyelinate regenerated axons. The different steps of SC development and their role in the maintenance of PNS integrity and regeneration after lesion are c…
NECAB2 participates in an endosomal pathway of mitochondrial stress response at striatal synapses
Synaptic signaling depends on ATP generated by mitochondria. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction and thus requires efficient mitochondrial quality control. We found that the neuronal calcium-binding protein NECAB2 ensures synaptic function in the striatum by increasing mitochondrial efficiency. NECAB2 associates with early endosomes and mitochondria at striatal synapses. Loss of NECAB2 dysregulates proteins of the endosomal ESCRT machinery and oxidative phosphorylation. Mitochondria from NECAB2-deficient mice are more abundant but less efficient. These mitochondria exhibit increased respiration and superoxide production but produ…