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Muskelin regulates actin filament- and microtubule-based GABA(A) receptor transport in neurons

Item Type:Article
Title:Muskelin regulates actin filament- and microtubule-based GABA(A) receptor transport in neurons
Creators Name:Heisler, F.F. and Loebrich, S. and Pechmann, Y. and Maier, N. and Zivkovic, A.R. and Tokito, M. and Hausrat, T.J. and Schweizer, M. and Bähring, R. and Holzbaur, E.L. and Schmitz, D. and Kneussel, M.
Abstract:Intracellular transport regulates protein turnover including endocytosis. Because of the spatial segregation of F-actin and microtubules, internalized cargo vesicles need to employ myosin and dynein motors to traverse both cytoskeletal compartments. Factors specifying cargo delivery across both tracks remain unknown. We identified muskelin to interconnect retrograde F-actin- and microtubule-dependent GABA(A) receptor (GABA(A)R) trafficking. GABA(A)Rs regulate synaptic transmission, plasticity, and network oscillations. GABA(A)R {alpha}1 and muskelin interact directly, undergo neuronal cotransport, and associate with myosin VI or dynein motor complexes in subsequent steps of GABA(A)R endocytosis. Inhibition of either transport route selectively interferes with receptor internalization or degradation. Newly generated muskelin KO mice display depletion of both transport steps and a high-frequency ripple oscillation phenotype. A diluted coat color of muskelin KOs further suggests muskelin transport functions beyond neurons. Our data suggest the concept that specific trafficking factors help cargoes to traverse both F-actin and microtubule compartments, thereby regulating their fate.
Keywords:Actin Cytoskeleton, Cell Adhesion Molecules, GABA-A Receptors, HEK293 Cells, Intracellular Signaling Peptides and Proteins, Microtubules, Neurons, Protein Transport, Animals, Mice
Publisher:Cell Press
Page Range:66-81
Date:14 April 2011
Official Publication:https://doi.org/10.1016/j.neuron.2011.03.008
PubMed:View item in PubMed

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