Another piece in the progranulin puzzle: special binding between progranulin and prosaposin creates additional lysosomal access

摘要

Abstract Loss‐of‐function mutations in the gene encoding the growth factor progranulin cause degeneration of the ageing brain in a dose‐dependent manner. While heterozygous mutations result in adult onset frontotemporal dementia, the much rarer homozygous null mutations cause an early onset lysosomal storage disorder. A better understanding of the biology of progranulin in the central nervous system is needed to find solutions for these incurable diseases. This Editorial highlights a study by Zhou et?al . in the current issue of the Journal of Neurochemistry , in which the authors provide data that are a step towards this goal. Progranulin is mainly expressed by neurons and microglia and, although it is a secreted protein, it also ends up in lysosomes. Recently, the trafficking of progranulin and the molecular players involved have become better understood. A special interaction between progranulin and its travelling companion, prosaposin, explains how both proteins can use each other's transport receptors to gain access to lysosomes.