Cell Biology

PolyQ caught in the act?

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Science  20 Oct 2017:
Vol. 358, Issue 6361, pp. 317-318
DOI: 10.1126/science.358.6361.317-c

Huntington's disease is a neurodegenerative disorder caused by the expanded polyglutamine (polyQ) repeat of mutant huntingtin (mHtt). PolyQ expansions result in protein aggregation into large neuronal inclusion bodies (IBs). These IBs are often regarded as protective deposits of toxic soluble species. Bäuerlein et al. used cryo-electron tomography to analyze the structure of mHtt IBs in mammalian cells and neurons under close-to-native conditions and at molecular resolution. The mHtt IBs consisted of radially arranged fibrils that closely interacted with cellular endomembranes, particularly the endoplasmic reticulum (ER). The interaction appeared to alter ER function and membrane dynamics at the IB periphery. Thus, rather than being inert deposits, mHtt IBs may mediate aspects of polyQ pathology.

Cell 171, 179 (2017).

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