Alternative splicing plasticity of the neurexin family of synaptic adhesion molecules in human sensory neurons

Human sensory neurons possess the ability to adapt the splicing of neurexin proteins, key regulators of synapse function, in response to various stimuli. Presynaptic neurexins (Nrxns) bind to numerous postsynaptic proteins in a splice-isoform dependent manner, thereby controlling synaptic connectivity, transmission, and plasticity.

Researchers have found that at splice site 4 (SS4) of Nrxn1 and Nrxn3, alternative splicing is plastic in human dorsal root ganglia (DRG) neurons, meaning it can change in response to environmental factors. This shift is observed in response to depolarization but not to sensitization with PGE2. Injuries to the central nervous system, such as axotomy, can also reduce alternative splicing at SS4 in DRG neurons.

Furthermore, the patterns of Nrxn alternative splicing within DRG neurons are dynamic during nervous system development and vary between neurons in the DRG, spinal cord, and cortex of adult animals. The study also reveals that exon use at SS4 is conserved between humans and mice for Nrxn1, but significantly different for other isoforms.

These findings suggest that Nrxn alternative splicing at SS4 in human and mouse DRG neurons may play a role in shaping somatosensory circuit wiring and synaptic function.