Short-chain fatty acid receptor GPR41-mediated activation of sympathetic neurons involves synapsin 2b phosphorylation

Synapsins are neuronal phosphoproteins that coat synaptic vesicles and are believed to function in the regulation of neurotransmitter release. The signaling mechanism for short-chain free fatty acid (SCFA)-stimulated NE release was examined using primary-cultured mouse sympathetic cervical ganglion neurons. Pharmacological and knockdown experiments showed that activation of sympathetic neurons by SCFA propionate involves SCFA receptor GPR41 linking to Gβγ-PLCβ3-ERK1/2-synapsin 2 signaling. Further, synapsin 2b directly interacts with activated ERK1/2 and can be phosphorylated on serine when SCFA activates sympathetic neurons.

► SCFAs increase NE release from primary-cultured sympathetic neurons via GPR41.
► Sympathetic activation by SCFA involves Gβγ, PLCβ3, ERK1/2, and synapsin 2.
► Synapsin 2 directly interacts with activated ERK1/2.
► Synapsin 2b can be phosphorylated when SCFA activates sympathetic neurons.