hrvatski

Toll-like receptor 2 deficiency is associated with specific alterations of synaptic proteome

Synaptic glycoprotein neuroplastin (Np) is a crucial synaptic junction (SJ) proteome member. Evidenced functions of Np include regulating Ca2+ clearance and its involvement in long-term potentiation. We have previously reported differential immunohistochemical pattern of Np across brain regions in Toll-like receptor 2 (TLR2) knock-out (KO) mice and assumed that detected alterations might accompany large-scale changes in the synaptic environment in TLR2KO mice. These findings guided us on a journey to address whether the absence of TLR2 affects the SJ proteome. The study was conducted on female and male mice with 4 wild types (WT) and 4 TLR2 KO per group. Tissue samples of the cortex, cerebellum, and hippocampus were isolated by neuroanatomical dissection and subjected to membrane fractionation protocol to obtain synaptic junction enriched fractions. Tryptic in- gel digestion was applied to the collected fraction, and generated peptides were analyzed by liquid chromatography-tandem mass spectrometry (LC- MS/MS). Data analysis revealed significant changes in protein abundance across all isolated brain regions and supported our previous results demonstrating alterations of Np and P-Type ATPases expression in TLR2KO mice. The most remarkable and sex-dependent differences in protein content were observed in the cortex of TLR2KO animals compared to WT, while a lesser extent of proteome disruption was shown in the hippocampus and cerebellum of TLR2KO animals. The protein systems that underwent significant modifications are particularly those implicated in neurotransmission, overall pre-and postsynaptic arrangements, synaptic energy metabolism, axon/dendrite cytoskeleton, and myelin sheath modifications. In conclusion, investigating a synaptic proteome in the TLR2KO mouse model enables a fresh look at the potential new roles of TLR2 in intercellular communication and neuronal connectivity in a sexspecific manner.

gangliosides ; Toll-like receptor ; neuroplastin ; P-type ATPases

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