1878-15512842014Feb24Dev CellThe GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development.381393381-9310.1016/j.devcel.2014.01.018S1534-5807(14)00059-8Regulation of cargo transport via adaptor molecules is essential for neuronal development. However, the role of PDZ scaffolding proteins as adaptors in neuronal cargo trafficking is still poorly understood. Here, we show by genetic deletion in mice that the multi-PDZ domain scaffolding protein glutamate receptor interacting protein 1 (GRIP1) is required for dendrite development. We identify an interaction between GRIP1 and 14-3-3 proteins that is essential for the function of GRIP1 as an adaptor protein in dendritic cargo transport. Mechanistically, 14-3-3 binds to the kinesin-1 binding region in GRIP1 in a phospho-dependent manner and detaches GRIP1 from the kinesin-1 motor protein complex thereby regulating cargo transport. A single point mutation in the Thr956 of GRIP1 in transgenic mice impairs dendritic development. Together, our results show a regulatory role for GRIP1 during microtubule-based transport and suggest a crucial function for 14-3-3 proteins in controlling kinesin-1 motor attachment during neuronal development.Copyright © 2014 Elsevier Inc. All rights reserved.GeigerJulia CJCInstitute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, 60438 Frankfurt am Main, Germany; Focus Program Translational Neurosciences (FTN), University of Mainz, 55131 Mainz, Germany.LipkaJoannaJCell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584CH Utrecht, the Netherlands; International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.SeguraInmaculadaIInstitute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, 60438 Frankfurt am Main, Germany.HoyerSusanneSInstitute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, 60438 Frankfurt am Main, Germany.SchlagerMax AMADepartment of Neuroscience, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.WulfPhebe SPSCell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584CH Utrecht, the Netherlands; Department of Neuroscience, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.WeingesStefanSInstitute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, 60438 Frankfurt am Main, Germany.DemmersJeroenJProteomics Center, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands.HoogenraadCasper CCCCell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584CH Utrecht, the Netherlands; Department of Neuroscience, Erasmus Medical Center, 3015GE Rotterdam, the Netherlands. Electronic address: c.hoogenraad@uu.nl.Acker-PalmerAmparoAInstitute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, 60438 Frankfurt am Main, Germany; Focus Program Translational Neurosciences (FTN), University of Mainz, 55131 Mainz, Germany. Electronic address: acker-palmer@bio.uni-frankfurt.de.engJournal ArticleResearch Support, Non-U.S. Gov't