STRA6, encoded by the stimulated by retinoic acid 6 gene, is a multifunctional membrane protein. It serves as a transmembrane pore for bidirectional vitamin A transport between extra-and intracellular retinoid binding proteins [2]. The process of vitamin A accumulation in cells is coupled with its esterification. STRA6 also functions as a ligand-activated cell surface signaling receptor, activating the JAK/STAT signaling pathway upon binding of holo-RBP, which is crucial for maintaining retinoid function in peripheral tissues and ensuring optimal vision [4].

In a denervation-induced muscle atrophy model, knockout of RBP4 alleviated fatty infiltration and muscle atrophy. Conversely, injection of retinol-bound holo-RBP4 aggregated these effects. Mechanistically, holo-RBP4 treatment increased STRA6 expression and promoted phosphorylation of downstream JAK2 and STAT3. Inhibition of the STRA6/JAK2/STAT3 pathway decreased the expression of muscle atrophy markers, suggesting that RBP4 promotes fat infiltration and muscle atrophy through a STRA6-dependent and JAK2/STAT3 pathway-mediated mechanism [1]. In thyroid carcinoma, STRA6-knockdown cells showed reduced proliferation and metastasis both in vitro and in vivo. STRA6 interacted with integrin-linked kinase (ILK) and activated the AKT/mTOR signaling pathway, contributing to thyroid carcinoma progression [3].

In conclusion, STRA6 is essential for vitamin A transport and cell signaling. Model-based research, such as gene knockout in mice, has revealed its role in muscle atrophy and thyroid carcinoma. Understanding STRA6 could potentially lead to new therapeutic strategies for these and other related diseases.

References:

1. Zhang, Kang-Zhen, Li, Jia-Wen, Xu, Jin-Shui, Rui, Yun-Feng, Gao, Wei. 2024. RBP4 promotes denervation-induced muscle atrophy through STRA6-dependent pathway. In Journal of cachexia, sarcopenia and muscle, 15, 1601-1615. doi:10.1002/jcsm.13518. https://pubmed.ncbi.nlm.nih.gov/39031684/

2. Kelly, Mary, von Lintig, Johannes. . STRA6: role in cellular retinol uptake and efflux. In Hepatobiliary surgery and nutrition, 4, 229-42. doi:10.3978/j.issn.2304-3881.2015.01.12. https://pubmed.ncbi.nlm.nih.gov/26312242/

3. He, Weiman, Cheng, Zhen, Huo, Zijun, Hong, Shubin, Xiao, Haipeng. . STRA6 Promotes Thyroid Carcinoma Progression via Activation of the ILK/AKT/mTOR Axis in Cells and Female Nude Mice. In Endocrinology, 164, . doi:10.1210/endocr/bqac215. https://pubmed.ncbi.nlm.nih.gov/36592123/

4. Noy, Noa. . Vitamin A Transport and Cell Signaling by the Retinol-Binding Protein Receptor STRA6. In Sub-cellular biochemistry, 81, 77-93. doi:. https://pubmed.ncbi.nlm.nih.gov/27830501/