Uncovering multiple axonal targeting pathways in hippocampal neurons

Dolora Wisco, Eric D. Anderson, Michael C. Chang, Caren Norden, Tatiana Boiko, Heike Fölsch, Bettina Winckler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Neuronal polarity is, at least in part, mediated by the differential sorting of membrane proteins to distinct domains, such as axons and somata/dendrites. We investigated the pathways underlying the subcellular targeting of NgCAM, a cell adhesion molecule residing on the axonal plasma membrane. Following transport of NgCAM kinetically, surprisingly we observed a transient appearance of NgCAM on the somatodendritic plasma membrane. Down-regulation of endocytosis resulted in loss of axonal accumulation of NgCAM, indicating that the axonal localization of NgCAM was dependent on endocytosis. Our data suggest the existence of a dendrite-to-axon transcytotic pathway to achieve axonal accumulation. NgCAM mutants with a point mutation in a crucial cytoplasmic tail motif (YRSL) are unable to access the transcytotic route. Instead, they were found to travel to the axon on a direct route. Therefore, our results suggest that multiple distinct pathways operate in hippocampal neurons to achieve axonal accumulation of membrane proteins.

Original languageEnglish (US)
Pages (from-to)1317-1328
Number of pages12
JournalJournal of Cell Biology
Volume162
Issue number7
DOIs
StatePublished - Sep 29 2003

Keywords

  • Axonal targeting
  • L1
  • Neuronal polarity
  • NgCAM
  • Transcytosis

ASJC Scopus subject areas

  • Cell Biology

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