Stage-Dependent Axon Transport of Proteasomes Contributes to Axon Development

被引：31

作者：

Hsu, Meng-Tsung ^{[1
]}

Guo, Chin-Lin ^{[2
]}

Liou, Angela Y. ^{[1
]}

Chang, Ting-Ya ^{[1
]}

Ng, Ming-Chong ^{[1
]}

Florea, Bogdan I. ^{[3
]}

Overkleeft, Herman S. ^{[3
]}

Wu, Yen-Lin ^{[1
]}

Liao, Jung-Chi ^{[4
]}

Cheng, Pei-Lin ^{[1
]}

机构：

[1] Acad Sinica, Inst Mol Biol, Taipei 11529, Taiwan

[2] Acad Sinica, Inst Phys, Taipei 11529, Taiwan

[3] Leiden Univ, Leiden Inst Chem, NL-2311 EZ Leiden, Netherlands

[4] Acad Sinica, Inst Atom & Mol Sci, Taipei 11529, Taiwan

来源：

DEVELOPMENTAL CELL | 2015年 / 35卷 / 04期

关键词：

26; S-PROTEASOME; NEURONAL POLARITY; PROTEIN; COMPLEX; SYSTEM; DYNEIN; PHOSPHORYLATION; ESTABLISHMENT; DEGRADATION; MOTILITY;

D O I：

10.1016/j.devcel.2015.10.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Axon extension at the growing tip requires elevated local protein supply, with a capability sustainable over long axons in varying environments. The exact mechanisms, however, remain elusive. Here we report that axon-promoting factors elicited a retrograde transport-dependent removal of proteasomes from nascent axon terminals, thereby increasing protein stability at axon tips. Such an effect occurred through phosphorylation of a dynein-interacting proteasome adaptor protein Ecm29. During the transition from immature neurites to nascent axons in cultured hippocampal neurons, live-cell imaging revealed a significant increase of the retrograde axonal transport of fluorescently labeled 20S proteasomes. This retrograde proteasome transport depended on neuron stage and increased with axon lengths. Blockade of retrograde transport caused accumulation of proteasomes, reduction of axon growth, and attenuation of growth-associated Par6 at the axon tip of newly polarized neurons. Our results delineate a regulatory mechanism that controls proteasome abundance via preferential transport required for axon development in newborn neurons.

引用

页码：418 / 431

页数：14

共 42 条

[1] Anterograde Transport of TrkB in Axons Is Mediated by Direct Interaction with Slp1 and Rab27 [J].