Huntingtin localisation studies - a technical review

It is well recognised that there are pitfalls when defining the subcellular localisation of a protein with immunocytochemistry. Accurate protein localisation to particular cellular micro-architecture is crucial in defining its role within the cell. Huntingtin (HTT), the protein mutated in the neurodegenerative disorder Huntington’s disease (HD) is a large protein of ill-defined function. Bearing little resemblance to other proteins, its function has been difficult to assign, therefore localising this protein with precision within the cell may provide further clues as to its normal and pathological function. Lack of consistency between methods employed in different studies has resulted in varying conclusions as to its subcellular localisation. This technical review investigates the effects that different immunocytological methods can have upon the apparent subcellular localisation of the huntingtin protein, and discusses the implications this may have.