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Kinesin-3 UNC-104 is the major transporter of synaptic vesicles and is activated by SYD-2. However, how SYD-2 binding to UNC-104 is controlled remains unknown. Here, we show that PTP-3 phosphatase is upstream of SYD-2 to regulate its intramolecular folding. Open conformation of SYD-2 scaffolds more UNC-104 along axons and boosts transport speeds.

PTP-3 phosphatase promotes intramolecular folding of SYD-2 to inactivate kinesin-3 UNC-104 in neurons