Tmod2, short for Tropomodulin 2, is an actin-regulating gene. It plays a crucial role in synapse maturation, dendritic arborization [3]. By binding to the pointed end of actin filaments via actin and tropomyosin binding sites, it regulates actin nucleation and polymerization, which is essential for the remodeling of cytoskeletal actin related to dendritic spine morphology-mediated synaptic plasticity [2].

In Tmod2 knockout mice, there are significant phenotypes related to cocaine-induced responses. These mice show attenuated sensitized locomotor responses to cocaine, indicating perturbed drug-induced plasticity. They also do not self-administer cocaine, lacking hedonic responses. Electrophysiological characterization reveals increased spontaneous firing rate of early postnatal and adult cortical and striatal neurons. In nucleus accumbens shell medium spiny neurons, cocaine-induced synaptic plasticity is either missing or reciprocal, suggesting Tmod2 is a major regulator of plasticity in the mesolimbic system and controls the reinforcing and addictive properties of cocaine [1].

In conclusion, Tmod2 is vital for neuronal development and synapse-related functions through its actin-regulating properties. The study of Tmod2 knockout mice has provided valuable insights into its role in cocaine-induced neuroadaptations, highlighting its potential as a therapeutic target for addiction-related disorders [1].

References:

1. Mitra, Arojit, Deats, Sean P, Dickson, Price E, Zhang, Zhong-Wei, Kumar, Vivek. 2024. Tmod2 Is a Regulator of Cocaine Responses through Control of Striatal and Cortical Excitability and Drug-Induced Plasticity. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 44, . doi:10.1523/JNEUROSCI.1389-23.2024. https://pubmed.ncbi.nlm.nih.gov/38508714/

2. Kuruba, Balaganesh, Starks, Nickolas, Josten, Mary Rose, Mikhaylova, Marina, Kostyukova, Alla S. 2023. Effects of Tropomodulin 2 on Dendritic Spine Reorganization and Dynamics. In Biomolecules, 13, . doi:10.3390/biom13081237. https://pubmed.ncbi.nlm.nih.gov/37627302/

3. Omotade, Omotola F, Rui, Yanfang, Lei, Wenliang, Fowler, Velia M, Zheng, James Q. 2018. Tropomodulin Isoform-Specific Regulation of Dendrite Development and Synapse Formation. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 38, 10271-10285. doi:10.1523/JNEUROSCI.3325-17.2018. https://pubmed.ncbi.nlm.nih.gov/30301754/