An activity-dependent local transport regulation via degradation and synthesis of KIF17 underlying cognitive flexibility

被引：9

作者：

Iwata, Suguru ^{[1
]}

Morikawa, Momo ^{[1
,2
]}

Takei, Yosuke ^{[3
]}

Hirokawa, Nobutaka ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Cell Biol & Anat, Bunkyo Ku, Tokyo 1130033, Japan

[2] RIKEN Ctr Brain Sci, Lab Mol Psychiat, Wako, Saitama 3510198, Japan

[3] Univ Tsukuba, Fac Med, Dept Anat & Neurosci, Tsukuba, Ibaraki 3058577, Japan

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 51期

基金：

日本学术振兴会;

关键词：

SYNAPTIC PROTEIN-DEGRADATION; MESSENGER-RNA; NMDA RECEPTOR; UBIQUITIN; TRANSLATION; MEMORY; PROTEASOME; PLASTICITY; LOCALIZATION; FLUORESCENT;

D O I：

10.1126/sciadv.abc8355

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Synaptic weight changes among postsynaptic densities within a single dendrite are regulated by the balance between localized protein degradation and synthesis. However, the molecular mechanism via these opposing regulatory processes is still elusive. Here, we showed that the molecular motor KIF17 was locally degraded and synthesized in an N-methyl-D-aspartate receptor (NMDAR)-mediated activity-dependent manner. Accompanied by the degradation of KIF17, its transport was temporarily dampened in dendrites. We also observed that activity-dependent local KIF1 7 synthesis driven by its 3' untranslated region (3'UTR) occurred at dendritic shafts, and the newly synthesized KIF17 moved along the dendrites. Furthermore, hippocampus-specific deletion of Kif17 3'UTR disrupted KIF17 synthesis induced by fear memory retrieval, leading to impairment in extinction of fear memory. These results indicate that the regulation of the KIF17 transport is driven by the single dendrite-restricted cycle of degradation and synthesis that underlies cognitive flexibility.

引用

页数：18