Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Bohn, G; Allroth, A; Brandes, G; Thiel, J; Glocker, E; Schäffer, AA; Rathinam, C; Taub, N; Teis, D; Zeidler, C; Dewey, RA; Geffers, R; Buer, J; Huber, LA; Welte, K; Grimbacher, B; Klein, C.
A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14.
NAT MED. 2007; 13(1): 38-45.
Doi: 10.1038/nm1528
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Thiel Jens
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- 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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