# SEA and GATOR 10 Years Later
## 9 Conclusions  
Since its discovery ten years ago, the SEA/GATOR complex has been recognized as an important regulator of the mTORC1 pathway that deals with the cell's response to amino acid and glucose availability, DNA damage, mitochondria impairment, etc. Many studies have also revealed the role of the SEA/GATOR complex in human diseases, especially in cancer and epilepsies. Despite the growing number of discoveries involving the SEA/GATOR complex in many organisms, a lot of questions concerning its function and the mechanisms leading to pathologies are still left unanswered. For example, the role of the GATOR complex in amino acid sensing and response has been already clarified in great detail in several studies; however, it is still unknown whether the SEA complex in yeast can perform sensing functions, given that many amino acid sensors interacting with GATOR are not conserved in yeast. The functions of the SEA complex in autophagy and in the formation of organelle contact sites have been extensively studied in yeast. Whether the GATOR complex has these functions in higher eukaryotes is currently unknown (Figure 5). Finally, the most intriguing problem at the moment concerns the molecular function of the SEACAT/GATOR2 complex, an enigma that has remained unresolved despite these 10 years of research and discoveries. Without any doubt, having a high-resolution structure of this subcomplex with or without its partners (SESTRINs, CASTOR2 and others) will be crucial for understanding its function. It will be also important to figure out the principles of interaction between the two SEA/GATOR subcomplexes in different organisms, which can shed light on how evolution shaped this assembly to adapt for the particular needs of various species. SEA members appeared earlier than GATOR members, similar to crocodiles, which are slightly older than alligators [215]. In the same way with crocodiles and alligators, SEA and GATOR are similar to each other in terms of size, structure (appearance) and function (behavior). On the other hand, both SEA and GATOR have a number of subtle yet significant differences that might be able to explain how they each adjusted to operate optimally in different organisms and environments. For example, as with crocodiles, which are bigger than alligators, SEA components are also bigger than their human homologues. Therefore, it will not be surprising if the structural studies reveal that the shape of the SEA complex will slightly differ from that of the GATOR complex, as the V-shape crocodiles' snout differs from larger U-shape snout of alligators. Despite the slight difference in shape, both reptiles use their snouts to effectively catch and hold the food. Similarly, SEA and GATOR complexes, despite several structural differences, can still respond to the presence of nutrients during regulation of the mTORC1 pathway.  
We are, therefore, confident that the next decade of SEA/GATOR research will lead to new exciting discoveries of the structure and function of this complex, that can better characterize its implication in health and diseases.  
This research was funded by La Ligue contre le Cancer 94 (Comite de Val-de-Marne). [PERSON] is a recipient of CONACYT PhD fellowship from Mexican government (Becas al extranjero N708006).  
Not applicable.  
We are grateful to [PERSON] for discussions and critical reading of manuscript.  
The authors declare no conflict of interest.