ハンチンチン蛋白質は傷害を受けた神経細胞内で重要なシグナル伝達分子と一緒に移動する可能性があることを発見 The huntingtin protein may travel together with important signaling molecules in injured neurons, researchers find
2022-09-27 バッファロー大学(UB)
In an injured neuron, HTT and Rab7 proteins move along a neuronal highway called an axon, traveling toward the cell body. HTT and Rab7 have each been tagged with different color markers, and they appear to be traveling together in a single compartment that is seen in yellow in this video. Experiments suggest that this HTT package may carry signaling molecules that “are essential for activating the production of proteins needed for neuron regeneration,” says University at Buffalo Shermali Gunawardena, senior author of a new study that reports on these findings. Credit: TJ Krzystek
HTTは、変異していない状態では、軸索と呼ばれる神経細胞の幹線道路に沿って、細胞の核に向かっても遠ざかっても規則正しく移動することが、これまでに明らかにされている。
研究では、これまでの研究成果を基に、核に向かう一方向に動く細胞区画におけるHHTTの未知の役割について詳しく説明した。この研究により、HHTTが神経細胞の損傷や再生に関与していることが示唆された。
ミバエの幼虫の神経細胞を傷つけると、HTTが損傷部位から細胞体へと移動することがわかった。HTTは、神経細胞の生存に必要な成分を、核があり、タンパク質が作られる細胞体に向かって運んでいるのだろう。
このHTTパッケージは、神経細胞の再生に必要なタンパク質の生産を活性化するのに不可欠なシグナル伝達分子を運んでいる可能性があることが実験で示された。
<関連情報>
- https://www.buffalo.edu/news/releases/2022/09/024.html
- https://www.tandfonline.com/doi/abs/10.1080/15548627.2022.2119351?journalCode=kaup20
軸索損傷時にHTT(ハンチンチン)とRAB7がシグナル伝達物質LAMP1を含む後期エンドソーム上で逆行性に共移動していること HTT (huntingtin) and RAB7 co-migrate retrogradely on a signaling LAMP1-containing late endosome during axonal injury
Thomas J. Krzystek,Joseph A. White,Rasika Rathnayake,Layne Thurston,Hayley Hoffmar-Glennon,Yichen Li & Shermali Gunawardena
Autophagy Published:09 Sep 2022
DOI:https://doi.org/10.1080/15548627.2022.2119351
ABSTRACT
HTT (huntingtin) is a 350-kDa protein of unknown function. While HTT moves bidirectionally within axons and HTT loss/reduction causes axonal transport defects, the identity of cargo-containing vesicles that HTT helps move remain elusive. Previously, we found an axonal retrogradely moving HTT-Rab7 vesicle complex; however, its biological relevance is unclear. Using Drosophila genetics, in vivo microscopy, membrane isolation and pharmacological inhibition, here we identified that adaptors Hip1 and Rilpl aid the retrograde motility of LAMP1-containing HTT-Rab7 late endosomes, not autophagosomes. Reduction of Syx17 and chloroquine- or bafilomycin A1-mediated pharmacological inhibition, but not reduction of Atg5, disrupted the in vivo motility of these vesicles. Further, because HTT-Rab7 vesicles colocalized with long-distance signaling components (BMP signaling: tkv-wit, injury: wnd) and move in a retrograde direction after Drosophila nerve crush, we propose that these vesicles likely traffic damage signals following axonal injury. Together, our findings support a previously unknown role for HTT in the retrograde movement of a Rab7-LAMP1-containing signaling late endosome.
