Reduction in synaptic vesicle proteins but increase in proteins involved in basic cell function in cerebral cortices without the endosomal SNARE proteins Vti1a and Vti1b

ABSTRACT: Absence of the endosomal SNAREs vti1a and vti1b results in perinatal death and severe neuronal phenotypes in mice while lack of one of these proteins results in minor phenotypes. Proteomic differences were investigated to obtain a deeper insight into processes in which Vti1a and Vti1b are involved. Here we applied a bottom-up shotgun proteomic approach to investigate the differences in wild-type, double heterozygous (DHET),vti1a vt1ib double knockout (DKO), vti1a knockout and vti1b knockout cerebral cortices. Single deletions did not affect protein levels. A total of 1725 proteins were detected of which 69 were down and 191 proteins were upregulated in DKO cortices. Many less abundant proteins belonged to the gene ontology terms and Reactome pathways synapse, synaptic vesicle cycle, vesicle mediated transport and L1CAM interaction in pathway enrichment analysis. More abundant proteins were enriched in Reactome- and KEGG-pathways such as spliceosome, ribosome, carbon metabolism and gene expression. Immunoblotting validated reduced expression levels of the tested synaptic vesicle proteins as well as increased amounts of lysophosphatidylcholine acyltransferase 1 (Lpcat1) and neuron-specific gene 2 (Nsg2 ), which is involved in postsynaptic AMPA-receptor recycling. These data indicate that the synapse and cell adhesion were strongly affected in DKO brains.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Embryo

SUBMITTER: Julia Voss  

LAB HEAD: Gabriele Fischer von Mollard

PROVIDER: PXD066845 | Pride | 2026-03-31

REPOSITORIES: Pride