MYL6, also known as myosin light chain 6, is an essential light chain of myosin. It plays a crucial role in supporting integrin αIIbβ3 activation in platelets, which is vital for processes like platelet spreading, aggregation, and clot retraction [3]. It may also contribute to the avidity modulation of integrin αIIbβ3 by binding to kindlin-3. Additionally, MYL6 is involved in the assembly of the sperm head-tail coupling apparatus through its interaction with cargo transport-related myosin proteins [4]. It is also associated with disulfidptosis, a newly identified mode of cell death [1,2,5,6,7,8].

In Myl6fl/flPF4-Cre mice with Myl6 deficiency in the megakaryocyte lineage, significant macrothrombocytopenia occurs due to defective proplatelet formation. Integrin αIIbβ3 activation and platelet aggregation are substantially impaired in these mice, and blood coagulation ability, as well as hemostatic and thrombotic functions, are also affected [3]. In the context of non-alcoholic fatty liver disease (NAFLD), high MYL6 expression in patients correlates with inflammation, oxidative stress, and disease severity, suggesting it could be a potential treatment target [1]. In sepsis-induced acute lung injury, MYL6 mRNA levels increase, and there is a causal relationship between MYL6 and sepsis, indicating its potential use in diagnosis and management [2].

In summary, MYL6 is essential for platelet-related functions, sperm formation, and is implicated in diseases such as NAFLD and sepsis-induced acute lung injury. Gene-knockout mouse models, like Myl6fl/flPF4-Cre mice, have been instrumental in revealing its role in specific biological processes and disease conditions, providing valuable insights for understanding disease mechanisms and potential therapeutic strategies.

References:

1. Luo, Xiaohua, Guo, Junjie, Deng, Hongbo, Si, Zhongzhou, Li, Jiequn. 2024. Unveiling the role of disulfidptosis-related genes in the pathogenesis of non-alcoholic fatty liver disease. In Frontiers in immunology, 15, 1386905. doi:10.3389/fimmu.2024.1386905. https://pubmed.ncbi.nlm.nih.gov/38812509/

2. Zhang, Anqi, Wang, Xinyang, Lin, Wen, Zhu, Haoqi, Pan, Jingyi. 2024. Identification and verification of disulfidptosis-related genes in sepsis-induced acute lung injury. In Frontiers in medicine, 11, 1430252. doi:10.3389/fmed.2024.1430252. https://pubmed.ncbi.nlm.nih.gov/39262873/

3. Xu, Zhen, Zhou, Ying, Yu, Hongyin, Chen, Xue, Ma, Yan-Qing. 2024. Myosin light chain 6 (Myl6) interacts with kindlin-3 and is required to support integrin αIIbβ3 activation in platelets in mice. In Journal of thrombosis and haemostasis : JTH, 22, 2009-2017. doi:10.1016/j.jtha.2024.01.007. https://pubmed.ncbi.nlm.nih.gov/38266679/

4. Gan, Shiming, Zhou, Shumin, Ma, Jinzhe, Ma, Meisheng, Yuan, Shuiqiao. 2024. BAG5 regulates HSPA8-mediated protein folding required for sperm head-tail coupling apparatus assembly. In EMBO reports, 25, 2045-2070. doi:10.1038/s44319-024-00112-x. https://pubmed.ncbi.nlm.nih.gov/38454159/

5. Liu, Hengrui, Tang, Tao. 2023. Pan-cancer genetic analysis of disulfidptosis-related gene set. In Cancer genetics, 278-279, 91-103. doi:10.1016/j.cancergen.2023.10.001. https://pubmed.ncbi.nlm.nih.gov/37879141/

6. Liu, Tingting, Kong, Xiangrui, Wei, Jianshe. 2024. Disulfidptosis: A New Target for Parkinson's Disease and Cancer. In Current issues in molecular biology, 46, 10038-10064. doi:10.3390/cimb46090600. https://pubmed.ncbi.nlm.nih.gov/39329952/

7. Zhang, Kangnan, Zhu, Zhenhua, Zhou, Jingyi, Yu, Fudong, Xu, Ling. 2024. Disulfidptosis-related gene expression reflects the prognosis of drug-resistant cancer patients and inhibition of MYH9 reverses sorafenib resistance. In Translational oncology, 49, 102091. doi:10.1016/j.tranon.2024.102091. https://pubmed.ncbi.nlm.nih.gov/39146597/

8. Cong, Yunyan, Cai, Guangyao, Ding, Chengcheng, Luo, Shiwei, Liu, Jihong. 2024. Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer. In Frontiers in genetics, 15, 1378907. doi:10.3389/fgene.2024.1378907. https://pubmed.ncbi.nlm.nih.gov/38694875/