658C Poster - 10. Cell biology: Cytoskeleton, organelles and trafficking
Saturday April 09, 1:30 PM - 3:30 PM
Dynein acts to cluster glutamate receptors and traffic the PIP5 kinase, Skittles, to regulate postsynaptic membrane organization at the neuromuscular junction
Authors: Amanda L. Neisch 1; Thomas Pengo 1; Adam W. Avery 1,2; Min-Gang Li 1; Thomas S. Hays 1
Affiliations: 1) University of Minnesota, Minneapolis, MN; 2) Oakland University, Rochester, MI
Keywords: a. cytoskeleton; f. neuromuscular junction
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. Using genetic, immunolocalization, and electrophysiology studies, we have identified distinct postsynaptic roles for dynein at neuromuscular junctions (NMJs). We have found that dynein punctae accumulate specifically on the postsynaptic side of glutamatergic synaptic terminals. Postsynaptic dynein is required for the localization of PI(4,5)P2, a phospholipid membrane component, and a number of membrane-associated proteins including components of the spectrin cytoskeleton. 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 and this localization is dynein dependent. Further, depletion of postsynaptic dynein results in enlarged ionotropic glutamate receptor (iGluR) clusters and an increased amplitude and frequency of mEJPs. PI(4,5)P2 levels do not affect iGluR clustering and dynein does not affect the levels of iGluR subunits at the NMJ, suggesting a unique transport independent function of dynein at the NMJ in clustering iGluRs. As dynein punctae closely associate with iGluR clusters, we propose that dynein physically stabilizes iGluRs at the postsynaptic membrane for proper synaptic transmission.