mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth

Abstract

Cell motility requires strict spatiotemporal control of protein expression. During cell migration, mRNA localization and local translation in subcellular areas like the leading edge and protrusions are particularly advantageous for regulating the reorganization of the cytoskeleton. Fidgetin-Like 2 (FL2), a microtubule severing enzyme (MSE) that restricts migration and outgrowth, localizes to the leading edge of protrusions where it severs dynamic microtubules. FL2 is primarily expressed during development but in adulthood, is spatially upregulated at the leading edge minutes after injury. Here, we show mRNA localization and local translation in protrusions of polarized cells are responsible for FL2 leading edge expression after injury. The data suggests that the RNA binding protein IMP1 is involved in the translational regulation and stabilization of FL2 mRNA, in competition with the miRNA let-7. These data exemplify the role of local translation in microtubule network reorganization during migration and elucidate an unexplored MSE protein localization mechanism. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/537087v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@139f4e5org.highwire.dtl.DTLVardef@1fd1a4eorg.highwire.dtl.DTLVardef@1ca17b4org.highwire.dtl.DTLVardef@da2b56_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe microtubule severing enzyme FL2 RNA is localized to the leading edge C_LIO_LIFL2 mRNA localization leads to FL2 translation within protrusions C_LIO_LIThe IMP family works in concert with Let-7 miRNA to regulate FL2 mRNA C_LI