UNC-16 alters DLK-1 localization and negatively regulates actin and microtubule dynamics in Caenorhabditis elegans regenerating neurons.
UNC-16 alters DLK-1 localization and negatively regulates actin and microtubule dynamics in Caenorhabditis elegans regenerating neurons.
复制标题
UNC-16 改变 DLK-1 定位并负向调节秀丽隐杆线虫再生神经元中的肌动蛋白和微管动力学。
DOI：
10.1093/genetics/iyab139
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发表时间：
2021
期刊：
影响因子：
3.3
通讯作者：
Koushika,SandhyaP
中科院分区：
文献类型：
--
作者：
Kulkarni,SuchetaS;Sabharwal,Vidur;Sheoran,Seema;Basu,Atrayee;Matsumoto,Kunihiro;Hisamoto,Naoki;Ghosh-Roy,Anindya;Koushika,SandhyaP
损伤后的神经元再生依赖于神经元的内在生长潜力。我们的研究表明，α-16，一种小杆线虫JIP 3同源物，通过调节再生起始和再生速率来抑制轴突再生。这通过抑制DLK-1的长同种型的再生促进活性而发生，并且独立于DLK-1的抑制性短同种型。我们发现，DLK-16以浓度依赖性方式促进DLK-1点状定位，限制了损伤后数分钟在切割部位DLK-1长亚型的可用性。β-16通过DLK-1负调节肌动蛋白动力学，部分通过DLK-1负调节微管动力学。我们发现unc-16突变体的损伤后细胞骨架动力学也部分依赖于CEBP-1。在unc-16突变体中看到的更快的再生并不导致功能恢复。我们的数据表明，抑制性控制由β-16和DLK-1的短亚型平衡的DLK-1的长亚型在vivo.We提出了一个模型，β-16的抑制作用，在再生中发生的内在的生长促进功能通过两个紧密的时间和空间控制DLK-1和细胞骨架动力学。
Neuronal regeneration after injury depends on the intrinsic growth potential of neurons. Our study shows that UNC-16, aCaenorhabditiselegansJIP3 homolog, inhibits axonal regeneration by regulating initiation and rate of regrowth. This occurs through the inhibition of the regeneration-promoting activity of the long isoform of DLK-1 and independently of the inhibitory short isoform of DLK-1. We show that UNC-16 promotes DLK-1 punctate localization in a concentration-dependent manner limiting the availability of the long isoform of DLK-1 at the cut site, minutes after injury. UNC-16 negatively regulates actin dynamics through DLK-1 and microtubule dynamics partially via DLK-1. We show that post-injury cytoskeletal dynamics inunc-16mutants are also partially dependent on CEBP-1. The faster regeneration seen inunc-16mutants does not lead to functional recovery. Our data suggest that the inhibitory control by UNC-16 and the short isoform of DLK-1 balances the intrinsic growth-promoting function of the long isoform of DLK-1in vivo.We propose a model where UNC-16’s inhibitory role in regeneration occurs through both a tight temporal and spatial control of DLK-1 and cytoskeletal dynamics.