Modulation of receptor cycling by neuron-enriched endosomal protein of 21 kD.
Although correct cycling of neuronal membrane proteins is essential for neurite outgrowth and synaptic plasticity, neuron-specific proteins of the implicated endosomes have not been characterized. Here we show that a previously cloned, developmentally regulated, neuronal protein of unknown function binds to syntaxin 13. We propose to name this protein neuron-enriched endosomal protein of 21 kD (NEEP21), because it is colocalized with transferrin receptors, internalized transferrin (Tf), and Rab4. In PC12 cells, NEEP21 overexpression accelerates Tf internalization and recycling, whereas its down-regulation strongly delays Tf recycling. In primary neurons, NEEP21 is localized to the somatodendritic compartment, and, upon N-methyl-d-aspartate (NMDA) stimulation, the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunit GluR2 is internalized into NEEP21-positive endosomes. NEEP21 down-regulation retards recycling of GluR1 to the cell surface after NMDA stimulation of hippocampal neurons. In summary, NEEP21 is a neuronal protein that is localized to the early endosomal pathway and is necessary for correct receptor recycling in neurons.
Steiner
Pascal
P
Faculté des Sciences de la Vie, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Sarria
J-C Floyd
JC
Glauser
Liliane
L
Magnin
Sarah
S
Catsicas
Stefan
S
Hirling
Harald
H
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002451:Cell Compartmentation; D003712:Dendrites / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D050765:Qa-SNARE Proteins; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism / Q000502:physiology*; D014168:Transferrin / Q000378:metabolism; D000077191:Wortmannin; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism
D000730:Androstadienes; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C461339:Nsg1 protein, rat; D011500:Protein Synthesis Inhibitors; D050765:Qa-SNARE Proteins; D018091:Receptors, AMPA; D011990:Receptors, Transferrin; D014168:Transferrin; D020126:Brefeldin A; D016202:N-Methylaspartate; D020695:rab4 GTP-Binding Proteins; C104722:glutamate receptor ionotropic, AMPA 2; D000077191:Wortmannin