Association of alpha B-crystallin, a small heat shock protein, with actin: Role in modulating actin filament dynamics in vivo

作者：Singh Bhairab N; Rao K Sridhar; Ramakrishna Tangirala; Rangaraj Nandini; Rao Ch Mohan^*

来源：Journal of Molecular Biology, 2007, 366(3): 756-767.

DOI：10.1016/j.jmb.2006.12.012

• alpha B-crystallin
• heat stress
• cytoskeletal stabilization
• actin
• pinocytosis

Disruption of cytoskeletal assembly is one of the early effects of any stress that can ultimately lead to cell death. Stabilization of cytoskeletal assembly, therefore, is a critical event that regulates cell survival under stress. alpha B-crystallin, a small heat shock protein, has been shown to associate with cytoskeletal proteins under normal and stress conditions. Earlier reports suggest that alpha B-crystallin could prevent stress-induced aggregation of actin in vitro. However, the molecular mechanisms by which alpha B-crystallin stabilizes actin filaments in vivo are not known. Using the H9C2 rat cardiomyoblast cell fine as a model system, we show that upon heat stress, alpha B-crystallin preferentially partitions from the soluble cytosolic fraction to the insoluble cytoskeletal protein-rich fraction. Confocal microscopic analysis shows that a-B-crystallin associates with actin filaments during heat stress and the extent of association increases with time. Further, immunoprecipitation experiments show that alpha B-crystallin interacts directly with actin. Treatment of heat-stressed H9C2 cells with the actin depolymerzing agent, cytochalasin B, failed to disorganize actin. We show that this association of a-B-crystallin with actin is dependent on its phosphorylation status, as treatment of cells with MAPK inhibitors SB202190 or PD98059 results in abrogation of this association. Our results indicate that alpha B-crystallin regulates actin filament dynamics in vivo and protects cells from stress-induced death. Further, our studies suggest that the association of alpha B-crystallin with actin helps maintenance of pinocytosis, a physiological function essential for survival of cells.

• 出版日期2007-2-23