Fig. 4.

Possible intracellular mechanisms of NMJ stabilization through a focus on actors interacting with cytoskeleton and organelles The dynamics and stability of both actin and microtubules regulate NMJ maintenance. Dynactin complex includes among others Arp1, p150glued and dyneins. Although present in both pre- and post-synaptic compartments, the TBCE protein accumulates at the Golgi apparatus and has been shown to be mainly required for maintenance of microtubules in distal axons so far. CLIPR-59 is located at the trans-Golgi network (TGN) and is proposed to affect protein/membrane trafficking or cytoskeleton remodeling at the NMJ, as well as in the pre-synaptic compartment, although its possible post-synaptic localization and role remain to be further analyzed. Molecular candidates have been proposed to act as synaptotoxic and synaptotrophic cues in NMJ stability: MMP3 and MMP9 located at the active terminals could cleave proBDNF at the active terminal during synaptic competition. The conversion of pro-brain-derived neurotrophic factor (proBDNF) to mature (m)BDNF would be activity-dependent and mediate synaptic competition and cell survival after endocytosis