کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1932450 1050582 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterisation of the interaction between syndecan-2, neurofibromin and CASK: Dependence of interaction on syndecan dimerization
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Characterisation of the interaction between syndecan-2, neurofibromin and CASK: Dependence of interaction on syndecan dimerization
چکیده انگلیسی

Neurofibromin and calcium/calmodulin-dependent serine protein kinase (CASK) are membrane-associated signalling and scaffolding proteins which are mutated in human genetic neurological disorders. Syndecan-2 is a highly glycosylated transmembrane protein whose intracellular C-terminus has previously been shown to interact with the post-synaptic density 95/discs large/zonula occludens-1 (PDZ) domain of CASK and with two separate regions of neurofibromin. These three proteins collaborate to orchestrate the induction of filopodia and dendritic spines. We have used systematic mutagenesis of the intracellular region of syndecan-2 and a quantitative yeast two-hybrid (Y2H) assay to study the determinants of their interactions. We show that syndecan’s interactions with both CASK and neurofibromin are dependent on syndecan homodimerization and that neurofibromin largely interacts with the membrane-proximal part of the dimeric syndecan intracellular domain, leaving the membrane-distal C-terminus free to interact with CASK. We conducted a phylogenetic study of syndecan sequences, finding correspondence between conserved residues and mutations affecting both dimerization and interactions; we also find that fish have a very different syndecan repertoire from tetrapods. Further Y2H screens reveal that syndecan-2 interacts with a third distinct region of neurofibromin, and that the multiple neurofibromin regions bind competitively, rather than co-operatively, to syndecan. We combine these results to propose a model for the ternary syndecan-neurofibromin-CASK complex.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 391, Issue 2, 8 January 2010, Pages 1216–1221
نویسندگان
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