Cloning and characterization of neuropilin-1-interacting protein: A PSD- 95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1

Huaibin Cai, Randall R. Reed

Research output: Contribution to journalArticle

Abstract

Neuropilin-1 (Npn-1), a receptor for semaphorin III, mediates the guidance of growth cones on extending neurites. The molecular mechanism of Npn-1 signaling remains unclear. We have used a yeast two-hybrid system to isolate a protein that interacts with the cytoplasmic domain of Npn-1. This Npn-1-interacting protein (NIP) contains a central PSD-95/Dlg/ZO-1 (PDZ) domain and a C-terminal-acyl carrier protein domain. The physiological interaction of Npn-1 and NIP is supported by co-immunoprecipitation of these two proteins in extracts from a heterologous expression system and from a native tissue. The C-terminal three amino acids of Npn-1 (S-E-A-COOH), which is conserved from Xenopus to human, is responsible for interaction with the PDZ domain-containing C-terminal two-thirds of NIP. NIP as well as Npn-1 are broadly expressed in mice as assayed by Northern and Western analysis. Immunohistochemistry and in situ hybridization experiments revealed that NIP expression overlaps with that of Npn-1. NIP has been independently cloned as RGS-GAIP-interacting protein (GIPC), where it was identified by virtue of its interaction with the C terminus of RGS-GAIP and suggested to participate in clathrin-coated vesicular trafficking. We suggest that NIP and GIPC may participate in regulation of Npn-1-mediated signaling as a molecular adapter that couples Npn-1 to membrane trafficking machinery in the dynamic axon growth cone.

Original languageEnglish (US)
Pages (from-to)6519-6527
Number of pages9
JournalJournal of Neuroscience
Volume19
Issue number15
StatePublished - Aug 1 1999

Keywords

  • Adapter protein
  • Axon guidance
  • Neuron development
  • Neuropilin-1
  • PDZ domain
  • Signal transduction
  • Yeast two-hybrid

ASJC Scopus subject areas

  • Neuroscience(all)

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