Human RAB2A blocking peptide

Ras-oncogenic pathway contributes to the pathogenesis of various tumours in humans, in which mutations of three canonical genes including H-Ras, N-Ras and K-Ras are the most common events. Dysregulation of Ras signalling can be tumourigenic, especially gliomas of the central nervous system. Rap proteins are members of the small GTPase superfamily that involved in many biological processes. However, it remains largely unclear as to whether and how Rap proteins are involved in the development of multiple gliomas. We found that the levels of the protein Rap2a and the activity of Rap2a (GTP-Rap2a) were weakly expressed in glioma tissues. Overexpressed Rap2a significantly inhibited the migration and invasion of glioma cells with an increase of GTP-Rap2a. Overexpression of the dominant-active (DA-Rap2a), but not the dominant-negative (DN-Rap2a) form of Rap2a, also similarly inhibited the migration and invasion of glioma cells by reducing the phosphorylation level of AKT. In contrast, downregulation of Rap2a promoted glioma migration and invasion, and raised the phosphorylation level of AKT, whereas these effects were inhibited by PI3K-specific inhibitor, LY294002. Thus unlike the other family members of Ras, Rab2a probably serves as a tumour suppressor in the pathogenesis of glioma.

Paneth cells play an important role in maintaining intestinal homeostasis by secreting a large number of antimicrobial peptides into the intestinal lumen. In this study, we found that Rip2 is required for lysozyme sorting in Paneth cells in a manner that is dependent on Nod2, LRRK2, and Rab2a. Rip2 deficiency in mouse led to lysosomal degradation of lysozyme in Paneth cells and prevented the recruitment of Rab2a onto dense core vesicles (DCVs). Like Nod2 and LRRK2, Rip2 localizes to DCVs in Paneth cells, and its DCV localization depends on Nod2 and LRRK2. Thus, we delineated a genetic pathway, consisting of Nod2 LRRK2 Rip2 Rab2a, which is required for lysozyme sorting. Taken together, our results indicate that the lysozyme-sorting process in Paneth cells is orchestrated by a number of host factors and highlight the importance of Paneth cell function in intestinal homeostasis.