Loss of 4E-BP converts cerebellar long-term depression to long-term potentiation

Autor: Natasha Saviuk, Yumaine Chong, Peng Wang, Sara Bermudez, Zhe Zhao, Arjun A. Bhaskaran, Derek Bowie, Nahum Sonenberg, Ellis Cooper, A. Pejmun Haghighi
Rok vydání: 2021
Předmět:
Zdroj: Cell reports. 39(10)
ISSN: 2211-1247
Popis: Genetic perturbances in translational regulation result in defects in cerebellar motor learning; however, little is known about the role of translational mechanisms in the regulation of cerebellar plasticity. We show that genetic removal of 4E-BP, a translational suppressor and target of mammalian target of rapamycin complex 1, results in a striking change in cerebellar synaptic plasticity. We find that cerebellar long-term depression (LTD) at parallel fiber-Purkinje cell synapses is converted to long-term potentiation in 4E-BP knockout mice. Biochemical and pharmacological experiments suggest that increased phosphatase activity largely accounts for the defects in LTD. Our results point to a model in which translational regulation through the action of 4E-BP plays a critical role in establishing the appropriate kinase/phosphatase balance required for normal synaptic plasticity in the cerebellum.
Databáze: OpenAIRE