Rescue of αB Crystallin (HSPB5) Mutants Associated Protein Aggregation by Co-Expression of HSPB5 Partners

摘要: HSPB5 (also called αB-crystallin) is a ubiquitously expressed small heat shock protein. Mutations in have been found to cause cataract, but are also associated with subgroup of myofibrillar myopathies. Cells expressing each these mutants characterized by the appearance protein aggregates primarily mutant HSPB5. Like several members HSPB family, can form both homo-oligomeric and hetero-oligomeric complexes. Previous studies showed that co-expression HSPB1 HSPB8 prevent aggregation (R120G) cardiomyocytes transgenic mice. In this study, we systematically compared effect human family (HSPB1-10) on three different (R120G, 450 Δ A, 464 CT). Of all members, HSPB1, HSPB4 itself, most effectively 3 mutants. HSPB6 were active less, whilst other 5 ineffective. Co-expression Hsp70 did not reduce mutants, suggesting aggregate formation likely related toxic gain function per se, rather loss chaperone oligomeric complexes containing (dominant negative effects). Our data suggest rescue due competitive incorporation its partners into hetero-oligomers hereby negating dominant effects functioning hetero-oligomer.