Disease-linked mutations in shank2 result in aberrant condensates: A Kitchen Table Talk
Автор: Dewpointx
Загружено: 2025-04-04
Просмотров: 198
New research from the Ditlev lab sheds light on how mutations in the postsynaptic density protein Shank2 impact local translation control in neurons—a mechanism increasingly linked to autism spectrum disorders.
Using reconstituted systems and patient-derived neurons, they found that Shank2 forms non-dynamic condensates with Homer1 at physiological concentrations. These structures sequester RNA-binding proteins like FMRP and suppress mRNA translation.
But here’s the twist: disease-linked mutations in Shank2’s intrinsically disordered region disrupt this function. Mutant condensates become more viscous and elastic, fail to properly enrich FMRP and RNA, and lose their ability to repress translation—leading to elevated protein production.
Even in heterozygous cells, these mutations are dominant—altering FMRP localization and translation of key synaptic proteins like CaMKII. This suggests a direct molecular mechanism for how Shank2 mutations may contribute to neurodevelopmental disorders.
This work bridges insights from immunology and neuroscience to highlight how biophysical properties of condensates shape brain function—and how their disruption can have far-reaching effects.
Доступные форматы для скачивания:
Скачать видео mp4
-
Информация по загрузке:
