title: Maturational conversion of dendritic early endosomes and their roles in L1-mediated axon growth.
abstract: The function of endosomes is intricately linked to cellular function in all cell types, including neurons. Intriguingly, neurons express cell type-specific proteins that localize to endosomes, but little is known about how these neuronal proteins interface with canonical endosomes and ubiquitously expressed endosomal components, such as EEA1 (Early Endosomal Antigen 1). NEEP21 (Neuronal Early Endosomal Protein 21 kDa) localizes to somatodendritic endosomes, and downregulation of NEEP21 perturbs the correct trafficking of multiple receptors, including glutamate receptors (GluA2) during LTP and amyloidogenic processing of βAPP. Our own work implicated NEEP21 in correct trafficking of the axonal cell adhesion molecule L1/neuron-glia cell adhesion molecule (NgCAM). NEEP21 dynamically localizes with EEA1-positive early endosomes but is also found in EEA1-negative endosomes. Live imaging reveals that NEEP21-positive, EEA1-negative endosomes arise as a consequence of maturational conversion of EEA1/NEEP21 double-positive endosomes. Interfering with EEA1 function causes missorting of L1/NgCAM, axon outgrowth defects on the L1 substrate, and disturbance of NEEP21 localization. Last, we uncover evidence that functional interference with NEEP21 reduces axon and dendrite growth of primary rat hippocampal neurons on L1 substrate but not on N-cadherin substrate, thus implicating endosomal trafficking through somatodendritic early endosomes in L1-mediated axon growth.
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908.
authors.forename: Zofia M
authors.initials: ZM
authors.lastname: Lasiecka
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908.
authors.forename: Chan Choo
authors.initials: CC
authors.lastname: Yap
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908.
authors.forename: Joshua
authors.initials: J
authors.lastname: Katz
authors.affiliation: Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22908 BWinckler@virginia.edu.
authors.forename: Bettina
authors.identifier: http://orcid.org/0000-0002-7924-9313
authors.initials: B
authors.lastname: Winckler
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; C461339:Nsg1 protein, rat; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1
keywords: NEEP21; NgCAM; Nsg-1; endosomes; live imaging; trafficking