中间纤维蛋白vimentin突变体e151k病理机制的分析细胞生物学专业论文.docxVIP

ABSTRACTVimentin ABSTRACT Vimentin is a highly conserved type III intermediate filament protein． Intermediate filament is a major component of cytoskeleton，working together with microtubules to support and maintain the normal positioning of cellular organelles，correct connection between cells and proper adhesion，as well as migration of vertebrate cells． Genetic cataract is one of the major causes for blindness． Mutations in the genes coding for structure proteins，transcription factors，membrane proteins and ion channels all cause genetic cataract．It has been shown that the point mutation G596A in the vimentin gene Can cause cataract． Mechanistically,the G596A mutation generates a protein with E151K nonsense change，causing a loss of vimentin assembly and leading to cataract formation．However,why E 1 5 1 K vimentin loses polymerization ability remains unknown． SUMOs are small Ubiquitin-like molecules．It can be linked to other proteins丽m the help of E 1，E2 and E3 ligases．This process is called sumoylation，which plays an important role in cellular physiology including protein-protein interaction，localization of subcellular organelles，protein binding of DNA and regulation of enzyme activities． Our laboratory has conducted comprehension research on sumoylation control of eye development，especially lens development in the past decade．Our results have demonstrated that sumo l—mediated sumoylation Ⅲ 万方数据 is is necessary to activate p32 Pax6 and thus regulate its downstream target genes to control eye development．In addition，our results have shown that sumo l。mediated sp l conjiugation enhances its transcription activity and promotes cell differentiation．In contrast，sum02／3一mediated sp l sumoylation suppresses its function and inhibits lens differentiation． Since the E 1 5 1 K mutation generates a conserved sumoylation site，we speculate that E 1 5 1 K vimentin may be s／maoylated and thus become incapable of assembling into functional intermediate filament，leading to a