The Role of Synaptic Cargo Transporters in Regulating Neuronal Excitation/Inhibition Balance in Autism Spectrum Disorders: A Focus on Syntabulin-syntaxin 1 A/B Axis

Abstract

Various cargo vesicles containing presynaptic proteins are transported from the neuronal cell body to the neuronal terminal to aid in active zone formation. Researchers showed altered levels up to 25 different synaptic proteins (SNAP47, GRIA3/4, GAP43, synaptotagmin 2, LRFN2, SV2C) and syntabulin. Syntabulin is a key component gene of a kinesin motor-adaptor complex essential for the forward movement of active zone components in axons. It plays a crucial role in the assembly of presynaptic structures during neuronal development in response to activity. However, the specific membranous cargoes and motor-cargo interactions are not fully understood. Recent research identified a syntaxin-1-binding protein called syntabulin. Syntabulin links syntaxin-containing vesicles to microtubules and moves with syntaxin in neuronal brain processes. Knocking down syntabulin expression or disrupting the syntabulin-syntaxin interaction hinders the attachment of syntaxin-cargo vesicles to microtubules and reduces syntaxin-1 distribution in neuronal processes. Conventional kinesin I heavy chain binds to syntabulin and associates with syntabulin-linked syntaxin vesicles in vivo. Syntabulin could act as a linker molecule that connects syntaxin-cargo vesicles to kinesin I, facilitating the transport of syntaxin-1 to neuronal processes. Syntabulin also regulates neuronal excitatory and inhibitory imbalance by transporting syntaxin 1 B, more than syntaxin 1A, to the presynaptic membrane. The gene for Syntabulin is found on human chromosome 8q23.2, in mouse on chromosome 15. This review shed light on the role of syntabulin-syntaxin 1A/B axis and mention different synaptic cargo transporters which could play any role in autism spectrum disorders. Further research should focus to study synaptopathies in autism spectrum disorders to open new arenas for pharmaceutical interventions.