کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2130968 1086613 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Desmin mutations in the terminal consensus motif prevent synemin-desmin heteropolymer filament assembly
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Desmin mutations in the terminal consensus motif prevent synemin-desmin heteropolymer filament assembly
چکیده انگلیسی

Disorganization of the desmin network is associated with cardiac and skeletal myopathies characterized by accumulation of desmin-containing aggregates in the cells. Multiple associations of intermediate filament proteins form a network to increase mechanical and functional stability. Synemin is a desmin-associated type VI intermediate filament protein. Neither its impact on desmin network nor how it integrates into desmin filament is yet elucidated. To gain more insight into the molecular basis of these processes, we coexpressed synemin with different desmin mutants in ex vivo models. The screening of fourteen desmin mutants showed that synemin with desmin mutants revealed two behaviors. Firstly, synemin was co-localized in desmin aggregates and its coexpression decreased the number of cells containing aggregates. Secondly, synemin was excluded from the aggregates, then synemin had no effect on desmin network organization. Among fourteen desmin mutants, there were only three mutants, p.E401K, p.R406W and p.E413K, in which synemin was not found in aggregates. This behavior was correlated to the abnormal salt-bridges of desmin-dimer as seen in silico constructs. Moreover, desmin constructs in silico and published results in literature have predicted that the salt-bridges absence in the desmin filament building prevent longitudinal annealing and/or radial compaction. These results suggest that the state of desmin-filament assembly is crucial for synemin anchorage and consequently might involve mechanical and functional stability of the cytoskeletal network.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 317, Issue 6, 1 April 2011, Pages 886–897
نویسندگان
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