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PMID: 18299352 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The somatodendritic endosomal regulator NEEP21 facilitates axonal targeting of L1/NgCAM.

The Journal of cell biology ·Vol. 180 ·No. 4 ·2008-02-25 ·Pages 827-42

Yap CC, Wisco D, Kujala P, Lasiecka ZM, Cannon JT, Chang MC, Hirling H, Klumperman J, Winckler B

Abstract

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.

MeSH Terms
Animals Axonal Transport/physiology Cell Adhesion/physiology Cell Adhesion Molecules, Neuron-Glia/metabolism Cell Differentiation/physiology Cells, Cultured Dendrites/metabolism,ultrastructure Down-Regulation/physiology Endocytosis/physiology Endosomes/metabolism,ultrastructure Fluorescent Antibody Technique Fluorescent Dyes Growth Cones/metabolism,ultrastructure Hippocampus/embryology,metabolism,ultrastructure Lysosomes/metabolism,ultrastructure Microscopy, Immunoelectron Nerve Tissue Proteins/metabolism Neural Cell Adhesion Molecule L1/metabolism Neural Pathways/embryology,metabolism,ultrastructure Protein Transport/physiology Rats
Chemicals
Cell Adhesion Molecules, Neuron-Glia Fluorescent Dyes Nerve Tissue Proteins Neural Cell Adhesion Molecule L1 Nsg1 protein, rat
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Yap Chan Choo
Department of Neuroscience, University of Virginia Medical School, Charlottesville, VA 22908, USA.
Wisco Dolora
Kujala Pekka
Lasiecka Zofia M
Cannon Johanna T
Chang Michael C
Hirling Harald
Klumperman Judith
Winckler Bettina
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200707143
Published
2008-02-25
Pages
827-42
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2265569
Subset
IM
Grants
NINDS NIH HHS · R01 NS045969 · United States
NINDS NIH HHS · 1R01NS 045969-06 · United States
External Links
PubMed source DOI: 10.1083/jcb.200707143 PMC Full Text View journal details
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