VAP spatially stabilizes dendritic mitochondria to locally support synaptic plasticity

• Published in: Nature communications Vol. 15; no. 1; p. 205
• Main Authors: Bapat, Ojasee, Purimetla, Tejas, Kruessel, Sarah, Shah, Monil, Fan, Ruolin, Thum, Christina, Rupprecht, Fiona, Langer, Julian D., Rangaraju, Vidhya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 13/109; 13/51; 13/89; 14; 14/1; 14/19; 14/34; 14/35; 14/69; 631/378/2591/2592; 631/378/87; 64; 64/86; 82/29; 82/58; 82/80; 82/83; Actin; Amyotrophic lateral sclerosis; Compartments; Cytoskeleton; Dendritic plasticity; Dendritic spines; Dendritic structure; Energy consumption; Humanities and Social Sciences; Membrane proteins; Membranes; Mitochondria; multidisciplinary; Neural plasticity; Plasticity; Proteins; Science; Science (multidisciplinary); Spine; Synapses; Synaptic plasticity; Synaptogenesis; Tethering
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-44233-8

Synapses are pivotal sites of plasticity and memory formation. Consequently, synapses are energy consumption hotspots susceptible to dysfunction when their energy supplies are perturbed. Mitochondria are stabilized near synapses via the cytoskeleton and provide the local energy required for synaptic plasticity. However, the mechanisms that tether and stabilize mitochondria to support synaptic plasticity are unknown. We identified proteins exclusively tethering mitochondria to actin near postsynaptic spines. We find that VAP, the vesicle-associated membrane protein-associated protein implicated in amyotrophic lateral sclerosis, stabilizes mitochondria via actin near the spines. To test if the VAP-dependent stable mitochondrial compartments can locally support synaptic plasticity, we used two-photon glutamate uncaging for spine plasticity induction and investigated the induced and adjacent uninduced spines. We find VAP functions as a spatial stabilizer of mitochondrial compartments for up to ~60 min and as a spatial ruler determining the ~30 μm dendritic segment supported during synaptic plasticity. Brain mitochondria serve as local energy supplies for synapses, and the mechanisms that stabilize mitochondria near dendritic spines are not fully understood. Here, the authors identify the vesicle-associated membrane protein-associated protein VAP as a mitochondrial stabilizer in spatially supporting synaptic plasticity.