TA PROTEIN INSERTION · Uncovering the Mammalian Targeting Machinery for Tail Anchored Proteins
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2009-12-01 → 2013-11-30
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-IRG
Линиите свързват координатора с партньорите.
Накратко на български
Механизмите за правилното насочване на протеини към митохондриите и комуникацията им с лизозомите се анализират чрез роботизирани системи. Разбирането на тези процеси помага да се разбере как се развиват стареенето и различни човешки заболявания.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Uncovering the Mammalian Targeting Machinery for Tail Anchored Proteins
Mitochondria generate the majority of cellular energy and house enzymes required for the synthesis, breakdown and interconversion of various species of amino acids, lipids, iron/sulfur clusters and other small molecules. Due to their diverse functions and essential roles in cellular metabolism, mitochondria serve as hubs for signaling in events such as growth, differentiation or cell death. Loss of optimal mitochondrial activity is therefore, non-surprisingly, implicated in a growing number of human diseases and in aging. The central tasks of mitochondria in cells necessitate that much care be invested in ensuring that mitochondrial proteins are targeted correctly and that mitochondria communicated constantly with the cellular environment. Using the IRG Marie Curie reintegration grant we have shown novel aspects regulating the correct composition of mitochondria and its ability to communicate with other organelles. Specifically, we have showed novel factors affecting protein-targeting to mitochondria (Papic et al, 2013; Krumpe et al, 2011), we have demonstrated how mitochondrial proteins can change over time and in various stresses (Breker et al, 2013) all how mitochondria can communicate directly with the storage organelles of the cell, the lysosomes/vacuoles (Alon et al, submitted). We have done all this with state of the art robotic set-up that enables us to perform biological experiments in high-throughput (Rimon&Schuldiner 2011).
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Activation of the BCL2 oncogene underlies a wide variety of malignant transformations. BCL2 must be present on the membranes of both the mitochondria and the endoplasmic reticulum (ER) to carry out its role in protecting cells from cell death (apoptosis). To enable its anchoring to intra cellular membranes, BCL2 has a C-terminal hydrophobic tail in a unique topology shared by members of a large family of Tail Anchored (TA) proteins. In mammals hundreds of such TA proteins exist that serve diverse and essential functions on every intracellular organelle. Despite the great importance of these proteins for cellular function, the pathway for enabling their anchoring to membranes has remained unknown for many years. We have recently discovered the protein machinery required for insertion of TA proteins into ER membranes in an effective and membrane specific manner in yeast. However, the mammalian pathway is not fully characterized. Moreover, the proteins required for insertion of TA proteins into mitochondrial membranes in both yeast and mammals are completely unknown. This proposal aims at uncovering and characterizing the machinery responsible for inserting BCL2 and other TA proteins into membranes in mammals. We will take two approaches – in the first, the homologous machinery to the GET complex in mammalian cells will be explored and its affect on BCL2 localization will be studied. In parallel, we will screen for components of the cellular machinery required for insertion of TA proteins into the mitochondria using high-throughput microscopy based silencing screens in mammalian cells. The discovery of the molecular machinery guiding the sub-cellular fate of the dual-localized BCL2 oncogene, can serve as a tool for better understanding BCL2 functions and for controlling its anti-apoptotic activity. More importantly, characterizing the basic machinery required for TA protein insertion will shed light on a fundamental and little explored part of cell biology.
Оригинален текст от CORDIS (на английски).
Участници
- WEIZMANN INSTITUTE OF SCIENCE · RehovotКоординаторИзраел
Връзки
Данни: CORDIS, © Европейски съюз