Pathway selection to the axon depends on multiple targeting signals in NgCAM

Chan Choo Yap, Rita L. Nokes, Dolora Wisco, Eric Anderson, Heike Fölsch, Bettina Winckler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Similar to most differentiated cells, both neurons and epithelial cells elaborate distinct plasma membrane domains that contain different membrane proteins. We have previously shown that the axonal cell-adhesion molecule L1/NgCAM accumulates on the axonal surface by an indirect transcytotic pathway via somatodendritic endosomes. MDCK epithelial cells similarly traffic NgCAM to the apical surface by transcytosis. In this study, we map the signals in NgCAM required for routing via the multi-step transcytotic pathway. We identify both a previously mapped tyrosine-based signal as a sufficient somatodendritic targeting signal, as well as a novel axonal targeting signal in the cytoplasmic tail of NgCAM. The axonal signal is glycine and serine rich, but only the glycine residues are required for activity. The somatodendritic signal is cisdominant and needs to be inactivated in order for the axonal signal to be executed. Additionally, we show that the axonal cytoplasmic signal promotes apical targeting in MDCK cells. Transcytosis of NgCAM to the axon thus requires the sequential regulated execution of multiple targeting signals.

Original languageEnglish (US)
Pages (from-to)1514-1525
Number of pages12
JournalJournal of cell science
Volume121
Issue number9
DOIs
StatePublished - May 1 2008

Keywords

  • Apical targeting
  • Axonal targeting
  • L1 cell-adhesion molecule
  • LDLR
  • MDCK cells
  • Transcytosis

ASJC Scopus subject areas

  • Cell Biology

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