Bipartite Interaction between Neurofibromatosis Type I Protein (Neurofibromin) and Syndecan Transmembrane Heparan Sulfate Proteoglycans

• DOI: 10.1523/jneurosci.21-11-03764.2001
• Publication Date: 2018-04-05T01:30:23Z
• Authors: Yi-Ping Hsueh; Anne M. Roberts; Manuela Volta; Morgan Sheng; Roland G. Roberts
• Keywords: Neurofibromin 1; Syndecan 1; Neurofibromatosis type I

The neurofibromatosis type 1 (NF1) gene encodes a large tumor suppressor protein (neurofibromin). Although it is known to possess Ras GTPase-activating (GAP) activity, the cellular role of neurofibromin remains unclear. Here we used yeast two-hybrid screening identify neurofibromin-interacting proteins. Syndecan-2, transmembrane heparan sulfate proteoglycan (HSPG), was isolated as binding partner for two distinct regions protein. We subsequently found that can bind all four mammalian syndecans. NF1 interaction requires domain and membrane-proximal region cytoplasmic tail syndecan, but not C terminus syndecan CASK, membrane-associated guanylate kinase (MAGUK). Neurofibromin, syndecans, CASK have overlapping subcellular distributions in axons synapses neurons, shown by biochemical fractionation immunostaining. Moreover, exists complex with vivo, evidenced their coimmunoprecipitation from rat brain. Our findings suggest different members family may be mechanism localizing specialized domains plasma membrane.