Allosteric stabilization of calcium and phosphoinositide dual binding engages several synaptotagmins in fast exocytosis.

ABSTRACT: Synaptic communication relies on the fusion of synaptic vesicles with the plasma membrane, which leads to neurotransmitter release. This exocytosis is triggered by brief and local elevations of intracellular Ca²⁺ with remarkably high sensitivity. How this is molecularly achieved is unknown. While synaptotagmins confer the Ca²⁺ sensitivity of neurotransmitter exocytosis, biochemical measurements reported Ca²⁺ affinities too low to account for synaptic function. However, synaptotagmin's Ca²⁺ affinity increases upon binding the plasma membrane phospholipid PI(4,5)P₂ and, vice versa, Ca²⁺ binding increases synaptotagmin's PI(4,5)P₂ affinity, indicating a stabilization of the Ca²⁺/PI(4,5)P₂ dual-b

SUBMITTER: Kobbersmed JRL 

PROVIDER: S-EPMC9489213 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature