Kv2-VAP interactions enhance presynaptic ER and mitochondrial calcium influx and the mobilization of vesicles from the reserve pool
Paton, C. D.; Hoppa, M. B.
Show abstract
In neurons, the endoplasmic reticulum (ER) forms an extensive network that establishes membrane contact sites (MCSs) with various organelles including the plasma membrane (PM). While MCSs are known to regulate lipid exchange and Ca2+ signaling, their specific roles in synaptic transmission remain poorly understood. Here, we demonstrate that the ER resident proteins VAPA and VAPB are essential for organizing presynaptic Ca2+ exchange and mobilizing synaptic vesicles. We show that the loss of VAP impairs Ca2+ loading into both the ER and mitochondria during electrical activity. This regulation occurs primarily through VAP interactions with voltage-gated potassium channels (Kv2) at the PM. Our data suggest that the Kv2-VAP complex organizes presynaptic Ca2+ signaling outside of the active zone. Without this scaffold, synaptic vesicles become trapped in the reserve pool and fail to participate in exocytosis. These findings reveal a novel role for Kv2-VAP MCSs in coordinating organelle Ca2+ signaling and the synaptic vesicle cycle.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Neurotransmitter release is triggered by a calcium-induced rearrangement in the Synaptotagmin-1/SNARE complex primary interface 97%
- Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo 96%
- Fully-primed slowly-recovering vesicles mediate presynaptic LTP at neocortical neurons 96%
Similar papers in this journal
- Clathrin-independent endocytic retrieval of SV proteins mediated by the clathrin adaptor AP-2 at mammalian central synapses 96%
- Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2 96%
- Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. 96%
Similar papers in this journal
Similar papers in this journal
- Steady-State Regulation of COPII-Dependent Secretory Cargo Sorting by Inositol Trisphosphate Receptors, Calcium, and Penta EF Hand Proteins 95%
- Functional investigation of a putative calcium-binding site involved in the inhibition of inositol 1,4,5-trisphosphate receptor activity 94%
- Disease-Linked Super-Trafficking of a Mutant Potassium Channel 94%
Similar papers in this journal
- Widely used CaMKII regulatory segment mutations cause tight actinin binding and dendritic spine enlargement in unstimulated neurons 96%
- Synaptotagmin 9 modulates spontaneous neurotransmitter release in striatal neurons by regulating substance P secretion 94%
- Single calcium channel nanodomains drive presynaptic calcium entry at individual lamprey reticulospinal presynaptic terminals 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.