TLS facilitates transport of mRNA encoding an actin-stabilizing protein to dendritic spines

Abstract

TLS (translocation in liposarcoma), an RNA-binding protein, was originally identified as a heterogeneous ribonuclear protein (hnRNP). Recently, we showed that TLS is localized in neuronal dendrites of mouse hippocampal neurons and is translocated to the spines, where local translation takes place, in an mGluR5 activation-dependent manner. However, the specific role of TLS has not been clarified. TLS-null neurons display abnormal spine morphology, suggesting that TLS-deficiency may impair activity-dependent actin reorganization in spines. To address this issue, we screened for mouse brain transcripts by their in vitro binding to TLS, and identified RNAs that associate with TLS, including mRNAs encoding actin-related proteins such as actin-stabilizing protein Nd1-L. Nd1-L transcripts were increased in the dendrites upon mGluR activation and significantly reduced in TLS-null dendrites. Overexpression of Nd1-L in mouse hippocampal neurons prevented damage to spine structure caused by actin destabilization. Our results demonstrate that TLS associates with mRNA encoding an actin-related protein and may be involved in actin reorganization in spines.