Gpm6b, also known as glycoprotein M6B, is a four-transmembrane protein belonging to the proteolipid protein family. It is widely expressed in neurons, oligodendrocytes, and astrocytes, and is involved in multiple biological processes such as neuronal differentiation, myelination, and the regulation of the serotonin transporter. It may also be associated with pathways like TGF-β-Smad2/3 signaling, which is important for smooth muscle cell differentiation [3,4,5,6].

In knockout (KO) mouse models, Gpm6b deficiency leads to impairment in sensorimotor gating and modulation of the behavioral response to a 5-HT2A/C receptor agonist [3]. A mutant allele of Gpm6b in mice causes deficits in delay discounting but enhances reward sensitivity, facilitating behavioral flexibility [4]. In addition, Gpm6b knockdown in vitro reduces the expression of inflammatory factors and matrix metalloproteinases in fibroblast-like synoviocytes from osteoarthritis patients, and Gpm6b knockout mice show its association with OA progression [1]. In prostate cancer cells, overexpression of Gpm6b inhibits cell proliferation, suggesting it as a tumor suppressor [2].

In conclusion, Gpm6b is involved in a variety of biological functions including neural-related behaviors, muscle cell differentiation, and responses in disease-related cells. Studies using KO mouse models have revealed its significance in sensorimotor gating, decision-making behaviors, and in diseases like osteoarthritis and prostate cancer, providing insights into potential therapeutic targets [1,2,3,4].

References:

1. Feng, Chongyang, Liu, Lin, Zhang, Jinxue, Li, Hongbo, Ding, Yong. 2024. Investigation of GPM6B as a novel therapeutic target in Osteoarthritis. In Arthritis research & therapy, 26, 200. doi:10.1186/s13075-024-03430-6. https://pubmed.ncbi.nlm.nih.gov/39533432/

2. He, Siyuan, Huang, Zhenlin, Li, Xiang, Liu, Bowen, Jia, Zhankui. 2020. GPM6B Inhibit PCa Proliferation by Blocking Prostate Cancer Cell Serotonin Absorptive Capacity. In Disease markers, 2020, 8810756. doi:10.1155/2020/8810756. https://pubmed.ncbi.nlm.nih.gov/33294057/

3. Dere, Ekrem, Winkler, Daniela, Ritter, Caroline, Ehrenreich, Hannelore, Werner, Hauke B. 2014. Gpm6b deficiency impairs sensorimotor gating and modulates the behavioral response to a 5-HT2A/C receptor agonist. In Behavioural brain research, 277, 254-63. doi:10.1016/j.bbr.2014.04.021. https://pubmed.ncbi.nlm.nih.gov/24768641/

4. Sanchez-Roige, Sandra, Barnes, Samuel A, Mallari, Jazlene, Polesskaya, Oksana, Palmer, Abraham A. 2022. A mutant allele of glycoprotein M6-B (Gpm6b) facilitates behavioral flexibility but increases delay discounting. In Genes, brain, and behavior, 21, e12800. doi:10.1111/gbb.12800. https://pubmed.ncbi.nlm.nih.gov/35243767/

5. Drabek, Ksenija, van de Peppel, Jeroen, Eijken, Marco, van Leeuwen, Johannes P T M. . GPM6B regulates osteoblast function and induction of mineralization by controlling cytoskeleton and matrix vesicle release. In Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 26, 2045-51. doi:10.1002/jbmr.435. https://pubmed.ncbi.nlm.nih.gov/21638316/

6. Zhang, Xiaomeng, Xie, Huaning, Chang, Pan, Wang, Shan, Tao, Ling. 2018. Glycoprotein M6B Interacts with TβRI to Activate TGF-β-Smad2/3 Signaling and Promote Smooth Muscle Cell Differentiation. In Stem cells (Dayton, Ohio), 37, 190-201. doi:10.1002/stem.2938. https://pubmed.ncbi.nlm.nih.gov/30372567/