Lsamp, the Limbic system-associated membrane protein, is a neural cell adhesion molecule of the IgLON family. It plays crucial roles in neurite outgrowth, synapse formation during development, and is involved in central nervous system development [1,2,5,7]. It may be associated with pathways related to neurotransmission and cell-cell interactions. Genetic models, especially mouse models, have been valuable in studying its functions.

In Lsamp-deficient mice, there are decreased social behavior, hyperactivity, decreased anxiety levels, and altered balance in GABAA receptor subunits [2]. They show lower sensitivity to amphetamine but higher sensitivity to cocaine and morphine, along with elevated serotonin function and turnover [2,3]. In the serotonergic neurotransmission system, Lsamp may impact the integrity of serotonergic synapses, as indicated by the response to escitalopram in Lsamp-deficient mice [4]. In lung cancer and neuroblastoma, down-regulation of LSAMP expression promotes cancer progression, suggesting its role as a tumor suppressor [6,7].

In conclusion, Lsamp is essential for normal neurotransmission-related behaviors and may be involved in maintaining the integrity of serotonergic synapses. The Lsamp-deficient mouse models have been instrumental in revealing its roles in psychiatric-like disorders and cancer progression, providing insights into potential therapeutic targets for these disease areas.

References:

1. Sharma, Kirti, Schmitt, Sebastian, Bergner, Caroline G, Mann, Matthias, Simons, Mikael. 2015. Cell type- and brain region-resolved mouse brain proteome. In Nature neuroscience, 18, 1819-31. doi:10.1038/nn.4160. https://pubmed.ncbi.nlm.nih.gov/26523646/

2. Bregin, Aleksandr, Mazitov, Timur, Aug, Ingrid, Innos, Jürgen, Vasar, Eero. 2019. Increased sensitivity to psychostimulants and GABAergic drugs in Lsamp-deficient mice. In Pharmacology, biochemistry, and behavior, 183, 87-97. doi:10.1016/j.pbb.2019.05.010. https://pubmed.ncbi.nlm.nih.gov/31163180/

3. Innos, Jürgen, Leidmaa, Este, Philips, Mari-Anne, Kõks, Sulev, Vasar, Eero. 2012. Lsamp⁻/⁻ mice display lower sensitivity to amphetamine and have elevated 5-HT turnover. In Biochemical and biophysical research communications, 430, 413-8. doi:10.1016/j.bbrc.2012.11.077. https://pubmed.ncbi.nlm.nih.gov/23206697/

4. Bregin, Aleksandr, Kaare, Maria, Jagomäe, Toomas, Philips, Mari-Anne, Vasar, Eero. 2020. Expression and impact of Lsamp neural adhesion molecule in the serotonergic neurotransmission system. In Pharmacology, biochemistry, and behavior, 198, 173017. doi:10.1016/j.pbb.2020.173017. https://pubmed.ncbi.nlm.nih.gov/32828972/

5. Philips, Mari-Anne, Lilleväli, Kersti, Heinla, Indrek, Innos, Jürgen, Vasar, Eero. 2014. Lsamp is implicated in the regulation of emotional and social behavior by use of alternative promoters in the brain. In Brain structure & function, 220, 1381-93. doi:10.1007/s00429-014-0732-x. https://pubmed.ncbi.nlm.nih.gov/24633737/

6. Chang, Chao-Yuan, Wu, Kuan-Li, Chang, Yung-Yun, Tsai, Ying-Ming, Hsu, Ya-Ling. 2021. The Downregulation of LSAMP Expression Promotes Lung Cancer Progression and Is Associated with Poor Survival Prognosis. In Journal of personalized medicine, 11, . doi:10.3390/jpm11060578. https://pubmed.ncbi.nlm.nih.gov/34202934/

7. Martinez-Monleon, Angela, Gaarder, Jennie, Djos, Anna, Kogner, Per, Fransson, Susanne. 2023. Identification of recurrent 3q13.31 chromosomal rearrangement indicates LSAMP as a tumor suppressor gene in neuroblastoma. In International journal of oncology, 62, . doi:10.3892/ijo.2023.5475. https://pubmed.ncbi.nlm.nih.gov/36601748/