Dataset Information

DDHD2 interacts with STXBP1 to mediate long-term memory via the generation of saturated free fatty acidsDDHD2 interacts with STXBP1 to mediate long-term memory via the generation of saturated free fatty acids

ABSTRACT: The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. Saturated FFAs, particularly myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the DDHD2 isoform of PLA1 in mice markedly reduced saturated FFAs across the brain and memory performance in reward-based learning and spatial memory models prior to the development of neuromuscular deficits. DDHD2 was shown to bind to the key synaptic protein STXBP1. Using STXBP1/2 knockout neurosecretory cells and a haploinsufficient STXBP1+/- mouse model of STXBP1 encephalopathy that is also associated with intellectual disability and motor dysfunction, we show that STXBP1 controls the targeting of DDHD2 to the plasma membrane and the generation of saturated FFAs in the brain. Our findings suggest key roles for DDHD2 and STXBP1 in the lipid metabolism underlying synaptic plasticity, learning and memory.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Adrenal Medulla Chromaffin Cell, Permanent Cell Line Cell

SUBMITTER: Benjamin Matthews

LAB HEAD: Frederic Meunier

PROVIDER: PXD047812 | Pride | 2024-05-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	DKO_GFP_Blank_pulldown.group	Other
	DKO_GFP_Blank_pulldown.wiff	Wiff
	DKO_GFP_Blank_pulldown.wiff.scan	Wiff
	DKO_GFP_Blank_pulldown__FDR.xlsx	Xlsx
	DKO_Munc18_pulldown_stim.group	Other

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Publications

The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids.

Akefe Isaac O IO Saber Saber H SH Matthews Benjamin B Venkatesh Bharat G BG Gormal Rachel S RS Blackmore Daniel G DG Alexander Suzy S Sieriecki Emma E Gambin Yann Y Bertran-Gonzalez Jesus J Vitale Nicolas N Humeau Yann Y Gaudin Arnaud A Ellis Sevannah A SA Michaels Alysee A AA Xue Mingshan M Cravatt Benjamin B Joensuu Merja M Wallis Tristan P TP Meunier Frédéric A FA

The EMBO journal 20240205 4

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of ...[more]

PMID: 38316990

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