Positive and negative regulations of cytoskeletal dynamism and neuronal lifespan

虽然我们在新制造的N-Shc和Grit/RICS双KO小鼠中探索了功能缺陷，但我们无法定义特定的表型。然而，在ShcB缺陷小鼠中，我们发现了小脑依赖性运动学习的独特变化，这与长期抑郁的减少以及浦肯野细胞内质网储存钙释放的缺陷有关。我们还研究了蛋白n端乙酰转移酶的辅助亚基Mdm20的潜在作用，发现Mdm20通过影响AKT的丝氨酸-473磷酸化来抑制自噬，从而促进polyQ聚集，AKT是调控细胞质蛋白质稳态的上游激酶。这些结果表明，神经富集的ShcB和Mdm20分别在神经元突触可塑性和蛋白质稳态中发挥独立作用。

While we explored functional deficits in the newly made N-Shc and Grit/RICS double KO mice, we were unable to define a specific phenotype. However, in ShcB deficient mice, we found a unique change in cerebellar-dependent motor learning, which was associated with reduced long-term depression as well as a deficit in calcium release from the endoplasmic reticulum store of Purkinje cells. We also examined a potential role of Mdm20, an auxiliary subunit of protein N-terminal acetyl transferase, and found that Mdm20 promotes polyQ aggregation via inhibiting autophagy through affecting serine-473 phosphorylation of AKT, an upstream kinase in the regulation of cytoplasmic proteostasis. These results suggest that neural enriched ShcB and Mdm20 play independent roles in neuronal synaptic plasticity and proteostasis, respectively.