Adaptation to stressors by Systemic Protein Amyloidogenesis

作者：Audas Timothy E; Audas Danielle E; Jacob Mathieu D; Ho J J David; Khacho Mireille; Wang Miling; Perera J Kishan; Gardiner Caroline; Bennett Clay A; Head Trajen; Kryvenko Oleksandr N; Jorda Merce; Daunert Sylvia; Malhotra Arun; Trinkle Mulcahy Laura; Gonzalgo Mark L; Lee Stephen^*

来源：Developmental Cell, 2016, 39(2): 155-168.

DOI：10.1016/j.devcel.2016.09.002

The amyloid state of protein organization is typically associated with debilitating human neuropathies and is seldom observed in physiology. Here, we uncover a systemic program that leverages the amyloidogenic propensity of proteins to regulate cell adaptation to stressors. On stimulus, cells assemble the amyloid bodies (A-bodies), nuclear foci containing heterogeneous proteins with amyloid-like biophysical properties. A discrete peptidic sequence, termed the amyloid-converting motif (ACM), is capable of targeting proteins to the A-bodies by interacting with ribosomal intergenic noncoding RNA (rIGSRNA). The pathological beta-amyloid peptide, involved in Alzheimer's disease, displays ACM-like activity and undergoes stimuli-mediated amyloidogenesis in vivo. Upon signal termination, elements of the heat-shock chaperone pathway disaggregate the A-bodies. Physiological amyloidogenesis enables cells to store large quantities of proteins and enter a dormant state in response to stressors. We suggest that cells have evolved a post-translational pathway that rapidly and reversibly converts native-fold proteins to an amyloid-like solid phase.

• 出版日期2016-10-24