The juxtamembrane linker of synaptotagmin 1 regulates Ca binding via liquid-liquid phase separation.

Synaptotagmin (syt) 1, a Ca sensor for synaptic vesicle exocytosis, functions in vivo as a multimer. Syt1 senses Ca via tandem C2-domains that are connected to a single transmembrane domain via a juxtamembrane linker. Here, we show that this linker segment harbors a lysine-rich, intrinsically disordered region that is necessary and sufficient to mediate liquid-liquid phase separation (LLPS).

The juxtamembrane linker of synaptotagmin 1 regulates Ca binding via liquid-liquid phase separation.

Synaptotagmin (syt) 1, a Ca sensor for synaptic vesicle exocytosis, functions as a multimer. Syt1 senses Ca via tandem C2-domains that are connected to a single transmembrane domain via a juxtamembrane linker. Here, we show that this linker segment harbors a lysine-rich, intrinsically disordered region that is necessary and sufficient to mediate liquid-liquid phase separation (LLPS).

Synaptic vesicle proteins are selectively delivered to axons in mammalian neurons.

Neurotransmitter-filled synaptic vesicles (SVs) mediate synaptic transmission and are a hallmark specialization in neuronal axons. Yet, how SV proteins are sorted to presynaptic nerve terminals remains the subject of debate. The leading model posits that these proteins are randomly trafficked throughout neurons and are selectively retained in presynaptic boutons.

Synaptotagmin 17 controls neurite outgrowth and synaptic physiology via distinct cellular pathways.

The synaptotagmin (syt) proteins have been widely studied for their role in regulating fusion of intracellular vesicles with the plasma membrane. Here we report that syt-17, an unusual isoform of unknown function, plays no role in exocytosis, and instead plays multiple roles in intracellular membrane trafficking. Syt-17 is localized to the Golgi complex in hippocampal neurons, where it coordinates import of vesicles from the endoplasmic reticulum to support neurite outgrowth and facilitate axon regrowth after injury.