Transmission of intracelular signals mediated by mTORC1

Habulin, Dunja (2014) Transmission of intracelular signals mediated by mTORC1. Bachelor's thesis, Faculty of Science > Department of Biology.

Language: Croatian

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mTORC1 complex is a very important part of signal pathways in the cell. Its discovery posed a variety of questions about its function. It is shown that mTORC1 complex has many duties in protein synthesis regulation, rybosome biogenesis, nutrient intake and autophagy, amino acids anabolism and cell energy status. A mild emphasis was put on mTORC1-LRS interaction for which is thought that enables amino acid presence sensing, especially leucine, in the cell cytoplasm. Except well known LRS leucilation function, it is discovered that LRS also has a major role in intracelular processes guided by mTORC1. Leucine has a key role in this signal pathway. When LRS binds Leu, LRS acts as a GAP for RagD-GTPase. Active form of Rag heterodimer ensures its interaction with mTORC1, which enables mTORC1 relocalization to the lysosome membrane. Another way of mTORC1 activation is by vacuolar ATPase. It is not established in the cytoplasm, but on the lysosome membrane. It is considered that this activation follows an „inside-out“ model by which amino acids are acumulated inside of lysosome, and v-ATPase is sensing them by a still unknown mechanism. v-ATPase controls interaction of Ragulator and Rag GTPase, and by that also the GEF function of Ragulator. Ragulator shows GEF activity for RagA and RagB proteins, since their GTP bound status is important for mTORC1 activation. Activated Rag complex binds to mTORC1 and recruits it to the lysosome membrane. It is assumed that mTORC1 is located near Rheb, because Rheb-GTP also stimulates mTORC1 activity. mTORC1 interacts with MAP4K3 kinase, which is activated by certain inductors and then can activate mTORC1 complex. Activated mTORC1 then activates S6K kinase which facilitates 40S subunit recruitment into active polysomes. There is also a PI3K/Akt pathway in which mTORC1 ensures phosphorilation of 4E-BP1, which then leaves EIF-4E, and by that, initiation of translation can occur. Both of the signal pathways have the same goal – to induce translation and enable protein synthesis which leads to cell growth. Besides activators there are also inhibitors of mTORC1. mTORC1 is named after one of its inhibitors - mammalian target of rapamycin. Thanks to rapamycin, mTORC1 was disovered. Recent studies indicate that rapamycin does not inhibit all of mTORC1 functions, but it is still unknown which of the pathways rapamycin inhibits. Ursolic acid is one of the inhibitors whose target is known – it inhibits lysosomal translocation of mTORC1 because UA interacts with Rag GTPases. Inhibitors of mTORC1 are used in tumor therapy, so they also have useful applications. Autofagy is another process which is coordinated by mTORC1 signal pathways, considering the fact that it promotes catabolic processes, which is opposite of mTORC1 duties – protein anaboly. Lot of characteristics of mTORC1 that are still unrevealed. For example, it is still not known which protein exactly senses amino acids, but there are lot of scientists interested in this theme and are actively researching. But, regardless of many unknowns, mTORC1 functions are more thoroughly researched than mTORC2. In this seminar not all of the mTORC1 functions and interactions were mentioned because there are too many. Processes that mTORC1 regulates, directly or indirectly, are very complex, therefore it is no surprise that it interacts with more proteins than it was described in this seminar.

Item Type: Thesis (Bachelor's thesis)
Supervisor: Gruić, Ita
Date: 2014
Number of Pages: 19
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 14 Nov 2014 10:56
Last Modified: 14 Nov 2014 10:56

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