Interferon-γ-inducible Rab20 regulates endosomal morphology and EGFR degradation in macrophages.

Little is known about the molecular players that regulate changes in the endocytic pathway during immune activation. Here we investigate the role of Rab20 in the endocytic pathway during activation of macrophages. Rab20 is associated with endocytic structures, but the function of this Rab GTPase in the endocytic pathway remains poorly characterized. We find that in macrophages, Rab20 expression and endosomal association significantly increase after interferon-γ (IFN-γ) treatment. Moreover, IFN-γ and Rab20 expression induce a dramatic enlargement of endosomes. These enlarged endosomes are the result of homotypic fusion promoted by Rab20 expression. The expression of Rab20 or the dominant-negative mutant Rab20T19N does not affect transferrin or dextran 70 kDa uptake. However, knockdown of Rab20 accelerates epidermal growth factor (EGF) trafficking to LAMP-2-positive compartments and EGF receptor degradation. Thus this work defines a function for Rab20 in the endocytic pathway during immune activation of macrophages

Unlocking the secrets of the genome

The primary objective of the Human Genome Project was to produce high-quality sequences not just for the human genome but also for those of the chief model organisms: Escherichia coli, yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans), fly (Drosophila melanogaster) and mouse (Mus musculus). Free access to the resultant data has prompted much biological research, including development of a map of common human genetic variants (the International HapMap Project)1, expression profiling of healthy and diseased cells2 and in-depth studies of many individual genes. These genome sequences have enabled researchers to carry out genetic and functional genomic studies not previously possible, revealing new biological insights with broad relevance across the animal kingdom 3, 4