BtaALTA0029325-1/2 @ bosTau6

The beta isoform (13-nt frameshift from HsaALTA0008403), which lacks a C-terminal PSD-95-binding motif ((S/T)XV), was more restricted to the postsynaptic density fraction than the motif-containing alpha1 isoform. The beta isoform did not interact with PSD-95 but specifically interacted with a nonphosphorylated alpha subunit of Ca(2+)/calmodulin-dependent protein kinase II through its unique C-terminal tail.

From the analysis using cultured neurons, unique expression of synGAP beta was found in a neuron with a sea urchin-like morphology, possibly a star pyramidal neuron, in which the synGAP beta expression was relatively high, in particular, at the distal part of its processes. SynGAP alpha1 was mostly or specifically localized to excitatory postsynaptic sites, whereas synGAP beta was present at both excitatory and inhibitory postsynaptic sites. Finally, there are more non-synaptic clusters in dendrites in the case of synGAP beta than synGAP alpha1.

alpha1 isoforms were always found enriched in the postsynaptic density, alpha2 isoforms changed from a non-synaptic to a mostly postsynaptic density localization with age and beta isoforms were always found enriched in non-synaptic locations.

SynGAP isoforms exhibit unique spatiotemporal expression patterns and play distinct roles in neuronal and synaptic development in mouse neurons. SynGAP-alpha1, which undergoes liquid-liquid phase separation with PSD-95, is highly enriched in synapses and is required for LTP. In contrast, SynGAP-beta (HsaALTA0008403, exon 18b), which does not bind PSD-95 PDZ domains, is less synaptically targeted and promotes dendritic arborization. A mutation in SynGAP-alpha1 that disrupts phase separation and synaptic targeting abolishes its ability to regulate plasticity and instead causes it to drive dendritic development like SynGAP-beta. Associated with APA usage.