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The endosomal pathway in neuronal dendrites is essential for membrane receptor trafficking and proper synaptic function and plasticity. However, the molecular mechanisms that organize specific endocytic trafficking routes are poorly understood. Here, we identify GRIP-associated protein-1 (GRASP-1) as a neuron-specific effector of Rab4 and key component of the molecular machinery that coordinates recycling endosome maturation in dendrites. We show that GRASP-1 is necessary for AMPA receptor recycling, maintenance of spine morphology, and synaptic plasticity. At the molecular level, GRASP-1 segregates Rab4 from EEA1/Neep21/Rab5-positive early endosomal membranes and coordinates the coupling to Rab11-labelled recycling endosomes by interacting with the endosomal SNARE syntaxin 13. We propose that GRASP-1 connects early and late recycling endosomal compartments by forming a molecular bridge between Rab-specific membrane domains and the endosomal SNARE machinery. The data uncover a new mechanism to achieve specificity and directionality in neuronal membrane receptor trafficking.
Pubmed ID: 20098723 RIS Download
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Netherlands Organization for Scientific Research (NWO) is a research institute and regional funding source in the Netherlands.
View all literature mentionsThe establishment of the European Science Foundation (ESF) in Strasbourg in 1974 was one of the earliest milestones on the road to achieving real cooperation in European research. The ESF began life with a membership of 42 academies and research councils in 15 countries; in 2011 it counts 78 Member Organizations (MOs), including research funding organizations, research performing organizations, academies and learned societies, in 30 countries. As an independent, non-governmental organization dedicated to pan-European scientific networking and collaboration, the ESF has had a key role to play in mediating between a multitude of heterogeneous research cultures and agencies. The ESF hosts an array of instruments to accommodate various types and levels of international collaboration, within Europe and beyond. The ESF''s unique characteristic in this area is its responsiveness to the scientific community, in contrast with the more targeted approaches taken by the European Commission. Many of the instruments operated by the ESF, e.g. Exploratory Workshops, EUROCORES (European Collaborative Research scheme), Research Networking Programmes (RNPs) and ESF Research Conferences, are designed to respond to needs articulated by the research community. Open calls for proposals are published on an annual basis, so that the themes for programmes, networks and workshops are gathered from the research community, in line with the ESF''s bottom-up principles. This is particularly welcome in research areas which might not otherwise be prioritized for funding on an international level. In recent years, the ESF''s profile has shifted from being mainly a facilitator of collaborative research and networking to also providing a platform for Member Organizations to develop joint strategic operations and synergy among themselves. By influencing the strategic agendas of MOs in this way, greater leverage over a much larger European budget and agenda is achieved. In other words, the ESF maximizes the impact of its support to the research community by combining bottom-up and topdown approaches to scientific cooperation.
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View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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