UNC-104 is the C. elegans homolog of kinesin-3 KIF1A known for its fast shuffling of STVs (synaptic vesicle protein transport vesicles) in axons. SYD-2 is the homolog of liprin-α in C. elegans known to activate UNC-104, however, signals that trigger SYD-2 binding to the motor remain unknown. Because SYD-2 is a substrate of PTP-3/LAR PTPR, we speculate a role of this phosphatase in SYD-2-mediated motor activation. Indeed, co-immunoprecipitation assays revealed increased interaction between UNC-104 and SYD-2 in ptp-3 knockout worms. Intramolecular FRET analysis in living nematodes demonstrates that SYD-2 largely exists in an open conformation state in ptp-3 mutants. These assays also revealed that non-phosphorylatable SYD-2 (Y741F) exists predominately in folded conformations while phosphomimicking SYD-2 (Y741E) primarily exists in open conformations. Increased UNC-104 motor clustering was observed along axons likely as a result of elevated SYD-2 scaffolding function in ptp-3 mutants. Also, both motor velocities as well as cargo transport speeds were visibly increased in neurons of ptp-3 mutants. Lastly, epistatic analysis revealed that PTP-3 is upstream of SYD-2 to regulate its intramolecular folding.

UNC-104 是kinesin-3 KIF1A 的秀丽隐杆线虫同源物，以其轴突中 STV（突触囊泡蛋白转运囊泡）的快速改组而闻名。SYD-2 是已知可激活 UNC-104 的秀丽隐杆线虫中 liprin-α 的同源物，然而，触发 SYD-2 与电机结合的信号仍然未知。因为 SYD-2 是 PTP-3/LAR PTPR 的底物，我们推测该磷酸酶在 SYD-2 介导的运动激活中的作用。事实上，共免疫沉淀试验揭示了ptp-3敲除蠕虫中UNC-104 和 SYD-2 之间的相互作用增加。活线虫的分子内 FRET 分析表明 SYD-2 在ptp-3 中主要以开放构象状态存在突变体。这些测定还表明，不可磷酸化的 SYD-2 (Y741F) 主要以折叠构象存在，而模拟磷酸化的 SYD-2 (Y741E) 主要以开放构象存在。沿轴突观察到 UNC-104 运动聚集增加，这可能是ptp-3突变体中SYD-2 支架功能升高的结果。此外，在ptp-3突变体的神经元中，运动速度和货物运输速度都明显增加。最后，上位分析显示 PTP-3 位于 SYD-2 的上游以调节其分子内折叠。