Intersectin and Endophilin condensates prime synaptic vesicles for release site replenishment.

Neurotransmitter is released from dedicated sites of synaptic vesicle fusion within a synapse. Following fusion, the vacated sites are replenished immediately by new vesicles for subsequent neurotransmission. These replacement vesicles are assumed to be located near release sites and used by chance.

Endophilin-A coordinates priming and fusion of neurosecretory vesicles via intersectin.

Endophilins-A are conserved endocytic adaptors with membrane curvature-sensing and -inducing properties. We show here that, independently of their role in endocytosis, endophilin-A1 and endophilin-A2 regulate exocytosis of neurosecretory vesicles. The number and distribution of neurosecretory vesicles were not changed in chromaffin cells lacking endophilin-A, yet fast capacitance and amperometry measurements revealed reduced exocytosis, smaller vesicle pools and altered fusion kinetics.

Regulation of synaptic vesicle acidification at the neuronal synapse.

The vacuolar H -adenosine triphosphatases (vATPases) acidify multiple intracellular organelles, including synaptic vesicles (SVs) and secretory granules. Acidification of SVs represents a critical point during the SV cycle: without acidification, neurotransmitters cannot be loaded into SVs. Despite the obvious importance of the vesicle acidification process for neurotrasmission and the life of complex organisms, little is known about the regulation of vATPase at the neuronal synapse.

Cells Control BIN1-Mediated Membrane Tubulation by Altering the Membrane Charge.

The Bridging integrator 1 (BIN1)/Amphiphysin/Rvs (BAR) protein family is an essential part of the cell's machinery to bend membranes. BIN1 is a muscle-enriched BAR protein with an established role in muscle development and skeletal myopathies. Here, we demonstrate that BIN1, on its own, is able to form complex interconnected tubular systems in vitro, reminiscent of t-tubule system in muscle cells.

Endophilin-A Deficiency Induces the Foxo3a-Fbxo32 Network in the Brain and Causes Dysregulation of Autophagy and the Ubiquitin-Proteasome System.

Endophilin-A, a well-characterized endocytic adaptor essential for synaptic vesicle recycling, has recently been linked to neurodegeneration. We report here that endophilin-A deficiency results in impaired movement, age-dependent ataxia, and neurodegeneration in mice. Transcriptional analysis of endophilin-A mutant mice, complemented by proteomics, highlighted ataxia- and protein-homeostasis-related genes and revealed upregulation of the E3-ubiquitin ligase FBXO32/atrogin-1 and its transcription factor FOXO3A.