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

Abstract

Cytoplasmic dynein is essential in motoneurons for retrograde cargo transport that sustains neuronal connectivity. Little, however, is known about dynein's function on the postsynaptic side of the circuit. Here we report distinct postsynaptic roles for dynein at neuromuscular junctions (NMJs). Intriguingly, we show that dynein punctae accumulate postsynaptically at glutamatergic synaptic terminals. Moreover, Skittles, a phosphatidylinositol 4-phosphate 5-kinase that produces PI(4,5)P2 to organize the spectrin cytoskeleton, also localizes specifically to glutamatergic synaptic terminals. Depletion of postsynaptic dynein disrupts the accumulation of Skittles, PI(4,5)P2 phospholipid, and organization of the spectrin cytoskeleton at the postsynaptic membrane. Coincidental with dynein depletion, we observe an increase in the size of ionotropic glutamate receptor (iGluRs) fields, and an increase in the amplitude and frequency of mEJPs. PI(4,5)P2 levels do not affect iGluR clustering, nor does dynein affect the levels of iGluR subunits at the NMJ. Our observations suggest a separate, transport independent function for dynein in iGluR cluster organization. Based on the close apposition of dynein punctae 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.