Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India.
Neurobiology, NCBS-TIFR, Bellary Road, Bengaluru 560 065, India.
Genetics. 2024 May 7;227(1). doi: 10.1093/genetics/iyae021.
Asymmetric transport of cargo across axonal branches is a field of active research. Mechanisms contributing to preferential cargo transport along specific branches in vivo in wild type neurons are poorly understood. We find that anterograde synaptic vesicles preferentially enter the synaptic branch or pause at the branch point in Caenorhabditis elegans Posterior Lateral Mechanosensory neurons. The synaptic vesicle anterograde kinesin motor UNC-104/KIF1A regulates this vesicle behavior at the branch point. Reduced levels of functional UNC-104 cause vesicles to predominantly pause at the branch point and lose their preference for turning into the synaptic branch. SAM-4/Myrlysin, which aids in recruitment/activation of UNC-104 on synaptic vesicles, regulates vesicle behavior at the branch point similar to UNC-104. Increasing the levels of UNC-104 increases the preference of vesicles to go straight toward the asynaptic end. This suggests that the neuron optimizes UNC-104 levels on the cargo surface to maximize the fraction of vesicles entering the branch and minimize the fraction going to the asynaptic end.
轴突分支的货物不对称运输是一个活跃的研究领域。在野生型神经元中，导致货物沿特定分支优先运输的机制还了解甚少。我们发现，在秀丽隐杆线虫的后外侧机械感觉神经元中，正向突触囊泡优先进入突触分支或在分支点暂停。突触囊泡正向运动蛋白 UNC-104/KIF1A 调节分支点处囊泡的这种行为。功能 UNC-104 水平降低会导致囊泡主要在分支点暂停，并失去进入突触分支的偏好。SAM-4/Myrlysin 有助于 UNC-104 在突触囊泡上的募集/激活，其对分支点处囊泡的行为调节类似于 UNC-104。增加 UNC-104 的水平会增加囊泡直接向非突触端前进的偏好。这表明神经元优化货物表面上 UNC-104 的水平，以最大化进入分支的囊泡比例，并最小化进入非突触端的囊泡比例。
