TY - JOUR T1 - The BLOC-1 Subunit Pallidin Facilitates Activity-Dependent Synaptic Vesicle Recycling JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0335-16.2017 SP - ENEURO.0335-16.2017 AU - Xun Chen AU - Wenpei Ma AU - Shixing Zhang AU - Jeremy Paluch AU - Wanlin Guo AU - Dion K. Dickman Y1 - 2017/01/30 UR - http://www.eneuro.org/content/early/2017/01/30/ENEURO.0335-16.2017.abstract N2 - Membrane trafficking pathways must be exquisitely coordinated at synaptic terminals to maintain functionality, particularly during conditions of high activity. We have generated null mutations in the Drosophila homolog of pallidin, a central subunit of the Biogenesis of Lysosome-related Organelles Complex 1 (BLOC-1), to determine its role in synaptic development and physiology. We find that Pallidin localizes to presynaptic microtubules and cytoskeletal structures, and that the stability of Pallidin protein is highly dependent on the BLOC-1 components Dysbindin and Blos1. We demonstrate that the rapidly recycling vesicle pool is not sustained during high synaptic activity in pallidin mutants, leading to accelerated rundown and slowed recovery. Following intense activity, we observe a loss of early endosomes and a concomitant increase in tubular endosomal structures in synapses without Pallidin. Together, our data reveals that Pallidin subserves a key role in promoting efficient synaptic vesicle recycling and re-formation through early endosomes during sustained activity.Significance Statement The speed and efficiency of synaptic vesicle recycling and re-formation are critical to maintain a functional synaptic vesicle pool during intense neuronal activity, yet the mechanisms that achieve this remain enigmatic. We show that the BLOC-1 component Pallidin promotes rapid and efficient synaptic vesicle recycling through endosomal intermediates. Further, Pallidin is necessary for the integrity of Rab5 positive synaptic endosomes during sustained neurotransmission. ER -