Compartmentalization of mRNA and translation by cell adhesions

Subcellular compartmentalization allows cells to concentrate and locally regulate functions. Here we identify translational compartmentalization in epidermal cells, with ribosomes, a subset of mRNAs, and the RNA-Induced Silencing Complex (RISC) being enriched at the cell cortex. We identify a crucial role for the desmosomal protein, desmoplakin, in directing ribosome localization and translation to the cortex. Transcript localization is also desmoplakin-dependent, but molecularly separable from ribosome recruitment. Analysis of local translation reveals that most of the cortical transcripts are translationally inhibited, while mRNAs for cell adhesion and the cytoskeleton are translationally active at the cortex under homeostatic conditions. Wounding induces translational changes, characterized by loss of RISC cortical localization and an increase in translation of RISC-associated transcripts, including cell adhesion mRNAs. Together our data demonstrate a desmosome-dependent cortical compartmentalization of mRNAs and translation that dynamically responds to barrier perturbations including wounding. Overall design: Comparison of total and cortical translatome in unwounded and wounded keratinocytes.