Dynein-driven regulation of postsynaptic membrane architecture and synaptic function.

Cytoplasmic dynein is essential in motor neurons for retrograde cargo transport that sustains neuronal connectivity. Little, however, is known about dynein function on the postsynaptic side of the circuit. Here, we report distinct postsynaptic roles for dynein at neuromuscular junctions in Drosophila. Intriguingly, we show that dynein puncta accumulate postsynaptically at glutamatergic synaptic terminals. Moreover, Skittles (Sktl), a phosphatidylinositol 4-phosphate 5-kinase that produces phosphatidylinositol 4,5-bisphosphate (PIP2) to organize the spectrin cytoskeleton, also localizes specifically to glutamatergic synaptic terminals. Depletion of postsynaptic dynein disrupted the accumulation of Skittles and the PIP2 phospholipid, and organization of the spectrin cytoskeleton at the postsynaptic membrane. Coincidental with dynein depletion, we observed an increase in the size of ionotropic glutamate receptor (iGluR) fields and an increase in the amplitude and frequency of miniature excitatory junctional potentials. PIP2 levels did not affect iGluR clustering, nor did dynein affect the levels of iGluR subunits at the neuromuscular junction. Our observations suggest a separate, transport-independent function for dynein in iGluR cluster organization. Based on the close apposition of dynein puncta to the iGluR fields, we speculate that dynein at the postsynaptic membrane contributes to the organization of the receptor fields, hence ensuring proper synaptic transmission.