Effects of Tropomodulin 2 on Dendritic Spine Reorganization and Dynamics.

Balaganesh Kuruba, Nickolas Starks, Mary Rose Josten, Ori Naveh, Gary Wayman, Marina Mikhaylova, Alla S Kostyukova

Biomolecules 2023 Aug 11

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Dendritic spines are actin-rich protrusions that receive a signal from the axon at the synapse. Remodeling of cytoskeletal actin is tightly connected to dendritic spine morphology-mediated synaptic plasticity of the neuron. Remodeling of cytoskeletal actin is required for the formation, development, maturation, and reorganization of dendritic spines. Actin filaments are highly dynamic structures with slow-growing/pointed and fast-growing/barbed ends. Very few studies have been conducted on the role of pointed-end binding proteins in the regulation of dendritic spine morphology. In this study, we evaluated the role played by tropomodulin 2 (Tmod2)-a brain-specific isoform, on the dendritic spine re-organization. Tmod2 regulates actin nucleation and polymerization by binding to the pointed end via actin and tropomyosin (Tpm) binding sites. We studied the effects of Tmod2 overexpression in primary hippocampal neurons on spine morphology using confocal microscopy and image analysis. Tmod2 overexpression decreased the spine number and increased spine length. Destroying Tpm-binding ability increased the number of shaft synapses and thin spine motility. Eliminating the actin-binding abilities of Tmod2 increased the number of mushroom spines. Tpm-mediated pointed-end binding decreased F-actin depolymerization, which may positively affect spine stabilization; the nucleation ability of Tmod2 appeared to increase shaft synapses.

Citation

Balaganesh Kuruba, Nickolas Starks, Mary Rose Josten, Ori Naveh, Gary Wayman, Marina Mikhaylova, Alla S Kostyukova. Effects of Tropomodulin 2 on Dendritic Spine Reorganization and Dynamics. Biomolecules. 2023 Aug 11;13(8)