Molecular Motors and their adaptors govern stress granule dynamics and composition

LORENA B BENSEÑOR; SHUO-CHIEN LING; SEBASTIAN MOON; VLADIMIR I GELFAND; GRACIELA L BOCCACCIO

Buenos Aires

Congreso; Argentinian Society of Biochemistry and Molecular Biology Research; 2013

SAIB

Stress granules (SGs) are discrete cytoplasmic ribonucleoparticles (RNPs) that store silenced mRNA and assemble transiently in response to cellular stress. SGs are highly dynamic, with mRNA and protein components shuttling in and out by mechanisms that involve mainly microtubule-based transport. Studies from our lab have shown that the molecular motors, cytoplasmic dynein and kinesin-1, are responsible for SGs assembly and disassembly, respectively. However, the selective transport of target mRNA molecules and their associated proteins (RBPs), remains elusive. We speculate that molecular motor?s adaptor proteins are responsible for such selection. Using Drosophila S2 cells together with RNAi technology and high-resolution confocal microscopy we found that Egalitarian (egl), but not Lisencephaly-1 (Lis1), two dynein adaptor proteins, are required for assembly of SGs. Conversely, Barentsz (Btz) and zipcode-binding protein (ZBP), adaptors of kinesin-1 are necessary for the timely dissolution of SGs. In addition, we observed that Fragile-X mental retardation protein (dFMRP) and Staufen-1, essential components of SGs are delivered by different adaptor proteins. Our data suggest that cargo-specific recruitment of adaptor proteins during SG formation is a key mechanism to maintain specificity in translation regulation during cellular stress.