A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14 - PubMed (original) (raw)

doi: 10.1038/nm1528. Epub 2006 Dec 31.

Anna Allroth, Gudrun Brandes, Jens Thiel, Erik Glocker, Alejandro A Schäffer, Chozhavendan Rathinam, Nicole Taub, David Teis, Cornelia Zeidler, Ricardo A Dewey, Robert Geffers, Jan Buer, Lukas A Huber, Karl Welte, Bodo Grimbacher, Christoph Klein

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A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14

Georg Bohn et al. Nat Med. 2007 Jan.

Abstract

Lysosome-related organelles have versatile functions, including protein and lipid degradation, signal transduction and protein secretion. The molecular elucidation of rare congenital diseases affecting endosomal-lysosomal biogenesis has given insights into physiological functions of the innate and adaptive immune system. Here, we describe a previously unknown human primary immunodeficiency disorder and provide evidence that the endosomal adaptor protein p14, previously characterized as confining mitogen-activated protein kinase (MAPK) signaling to late endosomes, is crucial for the function of neutrophils, B cells, cytotoxic T cells and melanocytes. Combining genetic linkage studies and transcriptional profiling analysis, we identified a homozygous point mutation in the 3' untranslated region (UTR) of p14 (also known as MAPBPIP), resulting in decreased protein expression. In p14-deficient cells, the distribution of late endosomes was severely perturbed, suggesting a previously unknown role for p14 in endosomal biogenesis. These findings have implications for understanding endosomal membrane dynamics, compartmentalization of cell signal cascades, and their role in immunity.

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