H2020Индивидуална стипендия2016–2018

MiroMigration · Miro dependent mitochondrial dynamics and the regulation of neuronal migration

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2016-04-04 → 2018-04-03
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Митохондриите в невроните се разполагат в зони с висока енергийна потребност, например в предната част на мигриращите клетки. Разбирането на този процес помага да се разбере как се развива мозъчната кора и защо при някои неврологични заболявания транспортът на енергия се нарушава.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Miro dependent mitochondrial dynamics and the regulation of neuronal migration

Regulated trafficking of mitochondria is essential for providing ATP at the correct spatial location to power neural computation, and for providing Ca2+ buffering at sites of Ca2+ entry or release. In neurons, the concentration of mitochondria in specific regions such as growth cones and synapses is important for correct neuronal function and development. Consequently, defective mitochondrial trafficking is increasingly implicated in neurological diseases. Very little is known regarding the role of mitochondrial positioning and function during neural development such as during the migration of cortical neurons. The mature cerebral cortex is made up of cell layers with distinct neuronal subtypes formed by a series of well-controlled cell migration and specification events. In mature neurons, mitochondria move around synaptic regions where they generate energy in the form of ATP and modulate synaptic calcium (Ca2+) concentration, which are essential for proper synaptic function and plasticity. The important phases of cortical development include neurogenesis and differentiation; neuronal migration and morphogenesis (i.e. multipolar to bipolar shape, movement of the nucleus) and synaptogenesis. During neuronal migration, newborn neurons generated from progenitors in the ventricular zone (VZ), migrate along radial glial fibers to populate the cortical plate (CP). In migrating neurons, mitochondria accumulate at specific subcellular regions where there are high energy demands (such as the cone of the leading process) but very little is known regarding the mechanisms that regulate their positioning and function during neuronal migration. The main objective was to make a major advancement in our understanding of the role of signalling- dependent positioning of mitochondria for the earliest stages of neuronal development that are key to determining correct neuronal connectivity. I have proposed to examine how the mitochondrial Rho GTPase (Miro) protein, acting as an essential adaptor for microtubule-dependent mitochondrial transport influences cortical neuronal migration. We aimed to characterise the impact of Miro deletion on the mitochondria positioning and functions in migrating neurons and also the consequence on the neuronal migration. We have identified a novel protein interaction impacting the neuronal migration and the mitochondrial trafficking.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Regulated trafficking of mitochondria is essential for providing ATP at the correct spatial location to power neural computation, and for providing Ca2+ buffering at sites of Ca2+ entry or release. In neurons, the concentration of mitochondria in specific regions such as growth cones and synapses is important for correct neuronal function and development. Consequently, defective mitochondrial trafficking is increasingly implicated in neurological diseases. Very little is known regarding the role of mitochondrial positioning and function during neural development such as during the migration of cortical neurons. This proposal will study the mechanisms that control the trafficking of mitochondria in neurons and how this regulates neuronal migration during cortex development. Using imaging, molecular techniques, combined with ex vivo or in utero electroporation and mouse transgenic models I will determine the molecular mechanisms underlying the signalling-dependent positioning of mitochondria in migrating neuronal progenitors. I will examine how the mitochondrial Ca2+-sensing GTPase Miro1 acts as a molecular switch to regulate mitochondrial positioning and function. How Miro1-mediated mitochondrial trafficking regulates neuronal migration in brain development will also be determined. A key goal will be to determine the role of Miro1 Ca2+-sensing and GTPase domains and other components of the Miro1 protein complex including CENPF, DISC1 and Nde1 in the control of mitochondrial positioning in these processes. These studies will significantly advance our understanding of the molecular mechanisms that control mitochondrial signalling-dependent localization in regulating neuronal development. Moreover, understanding these processes may highlight novel therapeutic approaches for neurodevelopmental disorders including Autism Spectrum Disorder, schizophrenia and intellectual disability, where disrupted neuronal migration and cortical wiring are thought to occur.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITY COLLEGE LONDON · LondonКоординаторОбединеното кралство