title: Dynein Regulator NDEL1 Controls Polarized Cargo Transport at the Axon Initial Segment.
abstract: The development and homeostasis of neurons relies heavily on the selective targeting of vesicles into axon and dendrites. Microtubule-based motor proteins play an important role in polarized transport; however, the sorting mechanism to exclude dendritic cargo from the axon is unclear. We show that the dynein regulator NDEL1 controls somatodendritic cargo transport at the axon initial segment (AIS). NDEL1 localizes to the AIS via an interaction with the scaffold protein Ankyrin-G. Depletion of NDEL1 or its binding partner LIS1 results in both cell-wide and local defects, including the non-polarized trafficking of dendritic cargo through the AIS. We propose a model in which LIS1 is a critical mediator of local NDEL1-based dynein activation at the AIS. By localizing to the AIS, NDEL1 facilitates the reversal of somatodendritic cargos in the proximal axon.
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Marijn
authors: M
authors: Kuijpers
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Dieudonnée
authors: D
authors: van de Willige
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Amélie
authors: A
authors: Freal
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Anaël
authors: A
authors: Chazeau
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Mariella A
authors: MA
authors: Franker
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Jasper
authors: J
authors: Hofenk
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Ricardo J Cordeiro
authors: RJ
authors: Rodrigues
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Lukas C
authors: LC
authors: Kapitein
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Anna
authors: A
authors: Akhmanova
authors: Department of Neuroscience, Erasmus Medical Center, 3015 CE Rotterdam, the Netherlands.
authors: Dick
authors: D
authors: Jaarsma
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands. Electronic address: c.hoogenraad@uu.nl.
authors: Casper C
authors: CC
authors: Hoogenraad
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D017487:Ankyrins; D002352:Carrier Proteins; C486015:Ndel1 protein, mouse; D004398:Dyneins
keywords: Ankyrin-G; NDE1; NDEL1; NudE; axon initial segment; cargo trafficking; dynein; neuron; polarized transport