Gorasp2, also known as Golgi reassembly stacking protein 2 or GRASP55, is a protein associated with the Golgi apparatus. It plays a crucial role in autophagy, an essential cellular process for maintaining homeostasis. Gorasp2 is involved in facilitating autophagosome-lysosome fusion, phagophore closure, and autophagosome maturation into autolysosomes, thereby regulating the autophagy pathway [1,2,6]. It also has a role in unconventional protein secretion, which is important for cell-environment communication [4]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable in further elucidating its functions.

Depletion of Gorasp2 in cell-based studies hindered phagophore closure by regulating the association between VPS4A and the ESCRT-III component, CHMP2A [1]. It also affected RAB7A activity by modulating its GEF complex, MON1A-CCZ1, and attenuated the assembly of SNARE complexes, all of which are important for autophagosome maturation [1]. In keratinocytes, impairment of autophagic flux by Gorasp2-related mechanisms alleviated psoriasis-like inflammation, suggesting its role in psoriatic skin inflammation [3]. Knockdown of Gorasp2 in primary human myometrial smooth muscle cells reduced cell contractility, and RNA sequencing analysis indicated it affects energy metabolism pathways and ATP production, showing its role in myometrial contractility during labor [5].

In conclusion, Gorasp2 is a multifunctional protein with key roles in autophagy and unconventional protein secretion. Model-based research, including KO or CKO mouse models, has revealed its significance in processes like autophagosome maturation, psoriatic skin inflammation, and myometrial contractility. Understanding Gorasp2 functions can potentially provide insights into treating autophagy-related diseases, psoriasis, and labor-related complications.

References:

1. Xing, Yusheng, Huang, Lei, Jian, Yannan, Wang, Yijie, Zhang, Xiaoyan. 2024. GORASP2 promotes phagophore closure and autophagosome maturation into autolysosomes. In Autophagy, 21, 37-53. doi:10.1080/15548627.2024.2375785. https://pubmed.ncbi.nlm.nih.gov/39056394/

2. Zhang, Xiaoyan, Wang, Leibin, Ireland, Stephen C, Zhang, Zhihai, Wang, Yanzhuang. 2019. GORASP2/GRASP55 collaborates with the PtdIns3K UVRAG complex to facilitate autophagosome-lysosome fusion. In Autophagy, 15, 1787-1800. doi:10.1080/15548627.2019.1596480. https://pubmed.ncbi.nlm.nih.gov/30894053/

3. Wang, Zhen, Zhou, Hong, Zheng, Huaping, Li, Wei, Li, Jiong. 2020. Autophagy-based unconventional secretion of HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inflammation. In Autophagy, 17, 529-552. doi:10.1080/15548627.2020.1725381. https://pubmed.ncbi.nlm.nih.gov/32019420/

4. Nüchel, Julian, Tauber, Marina, Nolte, Janica L, Demetriades, Constantinos, Plomann, Markus. 2021. An mTORC1-GRASP55 signaling axis controls unconventional secretion to reshape the extracellular proteome upon stress. In Molecular cell, 81, 3275-3293.e12. doi:10.1016/j.molcel.2021.06.017. https://pubmed.ncbi.nlm.nih.gov/34245671/

5. Yang, Fan, Chen, Lina, Wen, Bolun, Ji, Kaiyuan, Liu, Huishu. 2023. Golgi Reassembly Stacking Protein 2 Modulates Myometrial Contractility during Labor by Affecting ATP Production. In International journal of molecular sciences, 24, . doi:10.3390/ijms241210116. https://pubmed.ncbi.nlm.nih.gov/37373263/

6. Zhang, Xiaoyan, Wang, Yanzhuang. 2018. The Golgi stacking protein GORASP2/GRASP55 serves as an energy sensor to promote autophagosome maturation under glucose starvation. In Autophagy, 14, 1649-1651. doi:10.1080/15548627.2018.1491214. https://pubmed.ncbi.nlm.nih.gov/29973119/