Molecular Motors Regulate SG Dynamics.

LOSCHI M.,; SLOMIANSKY V; BOCCACCIO G.L.

Saxton River, Vermont, USA

Congreso; FASEB Summer Research Conferences- Intracellular mRNA transport and localized translation; 2009

FASEB

Molecular Motors Regulate SG Dynamics. Loschi M. (1,3), Slomiansky V. (1), Boccaccio G.L. (1,2,3) (1)Instituto Leloir; (2)Facultad de Ciencias Exactas y Naturales, University of Buenos Aires; (3)IIBBA-CONICET. Buenos Aires, Argentina The formation of cytoplasmic aggregates known as stress granules (SGs) harbouring abortive translation initiation complexes is a conserved hallmark of the stress response. SGs are transient, their assembly depends on the regulated aggregation of specific RNA-binding proteins and their disassembly requires the chaperone hsp70. P-bodies (PBs) are related cytoplasmic structures harboring silenced mRNAs. While SGs assemble transiently, PBs are constitutive and further induced by stress. We have investigated the role of molecular motors in SG and PB dynamics in response to stress. We found that impairment of retrograde transport by knockdown of mammalian dynein heavy chain 1 (DHC1) or bicaudal D1 (BicD1) inhibits SG formation without affecting protein synthesis blockage. Silencing of DHC1 also prevents PB growth upon stress. Conversely, impairment of anterograde transport by knockdown of kinesin heavy chain KIF5B or kinesin light chain 1 (KLC1) delayed SG dissolution. Simultaneous knockdown of dynein and kinesin reverts the effect of single knockdowns on both SGs and PBs, suggesting that a balance between antagonistic transports driven by these molecular motors governs foci formation and dissolution.  The role of dynein and kinesin is conserved in Drosophila cells. Finally, pharmacological and RNAi strategies indicate that p38 activates SG dissolution in both, mammalian and Drosophila cells. Supported by CONICET, UBA and ANPCyT, Argentina and NIH, USA