TMEM106B p.T185S regulates TMEM106B protein levels: implications for frontotemporal dementia (pages 781–791)
Alexandra M. Nicholson, NiCole A. Finch, Aleksandra Wojtas, Matt C. Baker, Ralph B. Perkerson III, Monica Castanedes-Casey, Linda Rousseau, Luisa Benussi, Giuliano Binetti, Roberta Ghidoni, Ging-Yuek R. Hsiung, Ian R. Mackenzie, Elizabeth Finger, Bradley F. Boeve, Nilüfer Ertekin-Taner, Neill R. Graff-Radford, Dennis W. Dickson and Rosa Rademakers
Version of Record online: 1 JUL 2013 | DOI: 10.1111/jnc.12329
We studied the p.T185S TMEM106B genetic variant previously implicated in frontotemporal dementia with TAR DNA binding protein 43 pathology caused by progranulin mutations. Our cell culture studies provide evidence that the protective S185 isoform is degraded more rapidly than T185 TMEM106B, potentially due to differences in glycosylation. These findings suggest that low TMEM106B levels might protect against FTLD-TDP in these patients.