The somatodendritic endosomal regulator NEEP21 facilitates axonal targeting of L1/NgCAM.
Correct targeting of proteins to axons and dendrites is crucial for neuronal function. We showed previously that axonal accumulation of the cell adhesion molecule L1/neuron-glia cell adhesion molecule (NgCAM) depends on endocytosis (Wisco, D., E.D. Anderson, M.C. Chang, C. Norden, T. Boiko, H. Folsch, and B. Winckler. 2003. J. Cell Biol. 162:1317-1328). Two endocytosis-dependent pathways to the axon have been proposed: transcytosis and selective retrieval/retention. We show here that axonal accumulation of L1/NgCAM occurs via nondegradative somatodendritic endosomes and subsequent anterograde axonal transport, which is consistent with transcytosis. Additionally, we identify the neuronal-specific endosomal protein NEEP21 (neuron-enriched endosomal protein of 21 kD) as a regulator of L1/NgCAM sorting in somatodendritic endosomes. Down-regulation of NEEP21 leads to missorting of L1/NgCAM to the somatodendritic surface as well as to lysosomes. Importantly, the axonal accumulation of endogenous L1 in young neurons is also sensitive to NEEP21 depletion. We propose that small endosomal carriers derived from somatodendritic recycling endosomes can serve to redistribute a distinct set of membrane proteins from dendrites to axons.
Yap
Chan Choo
CC
Department of Neuroscience, University of Virginia Medical School, Charlottesville, VA 22908, USA.
Wisco
Dolora
D
Kujala
Pekka
P
Lasiecka
Zofia M
ZM
Cannon
Johanna T
JT
Chang
Michael C
MC
Hirling
Harald
H
Klumperman
Judith
J
Winckler
Bettina
B
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D019062:Cell Adhesion Molecules, Neuron-Glia / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D015536:Down-Regulation / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009434:Neural Pathways / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology; D051381:Rats
D019062:Cell Adhesion Molecules, Neuron-Glia; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; C461339:Nsg1 protein, rat