mislocalization

Mislocalization is the incorrect localization of biological molecules or structures within a cell, tissue, or organism. It most commonly refers to proteins or RNAs that fail to reach their normal site of action, but can also include lipids, organelles, or signaling components. Mislocalization can occur during development, normal physiology under stress, or in disease.

Causes of mislocalization include mutations that alter localization signals, defects in transport machinery such as nuclear import/export receptors or vesicular trafficking pathways, and post-translational modifications that change targeting. Cellular stress, aging, or protein misfolding can also disrupt compartmental boundaries and trap molecules in inappropriate locations, leading to abnormal interactions or aggregation.

The consequences of mislocalization are varied and depend on the molecule and context. They can include loss of function because a protein or RNA is not where it is required, unintended interactions in the wrong compartment, or constitutive activity of pathways that should be inactive in that location. Mislocalization is implicated in several diseases, notably in neurodegenerative conditions where key proteins accumulate outside their normal sites, and in cancer where tumor suppressors or signaling components are diverted from their functional compartments.

Examples commonly discussed in the literature include the mislocalization of tau protein from axons to somatodendritic regions in Alzheimer's disease, and the cytoplasmic mislocalization of RNA-binding proteins such as TDP-43 in ALS. In cancer research, altered localization of tumor suppressors like PTEN can contribute to oncogenic signaling.

Detection and study of mislocalization rely on imaging techniques, such as fluorescent tagging and immunostaining, as well as biochemical fractionation and functional rescue experiments to determine the consequences of altered localization.