Bipartite interaction between neurofibromatosis type I protein (neurofibromin) and syndecan transmembrane heparan sulfate proteoglycans.

The neurofibromatosis type 1 (NF1) gene encodes a large tumor suppressor protein (neurofibromin). Although it is known to possess Ras GTPase-activating protein (GAP) activity, the cellular role of neurofibromin remains unclear. Here we used yeast two-hybrid screening to identify neurofibromin-interacting proteins. Syndecan-2, a transmembrane heparan sulfate proteoglycan (HSPG), was isolated ...
as a binding partner for two distinct regions of the neurofibromin protein. We subsequently found that neurofibromin can bind all four mammalian syndecans. NF1 interaction requires the transmembrane domain and a membrane-proximal region of the cytoplasmic tail of syndecan, but not the C terminus of syndecan known to bind to CASK, a membrane-associated guanylate kinase (MAGUK). Neurofibromin, syndecans, and CASK have overlapping subcellular distributions in axons and synapses of neurons, as shown by biochemical fractionation and immunostaining. Moreover, neurofibromin exists in a complex with syndecan and CASK in vivo, as evidenced by their coimmunoprecipitation from rat brain. Our findings suggest that interaction with different members of the syndecan family may be a mechanism for localizing neurofibromin to specialized domains of the plasma membrane.
Mesh Terms:
Animals, Brain, Brain Chemistry, Calcium-Calmodulin-Dependent Protein Kinases, Guanylate Kinases, Heparan Sulfate Proteoglycans, Humans, Macromolecular Substances, Membrane Glycoproteins, Nerve Tissue Proteins, Neurofibromatosis 1, Neurofibromin 1, Nucleoside-Phosphate Kinase, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proteoglycans, Rats, Saccharomyces, Subcellular Fractions, Syndecan-2, Syndecan-3, Syndecans, Two-Hybrid System Techniques
J. Neurosci.
Date: Jun. 01, 2001
Download Curated Data For This Publication
199233
Switch View:
  • Interactions 5