Muskelin regulates actin filament- and microtubule-based GABA(A) receptor transport in neurons.
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Muskelin regulates actin filament- and microtubule-based GABA(A) receptor transport in neurons. / Heisler, Frank; Löbrich, Sven; Pechmann, Yvonne; Maier, Nikolaus; Zivkovic, Aleksandar R; Tokito, Mariko; Hausrat, Torben; Schweizer, Michaela; Bähring, Robert; Holzbaur, Erika L F; Schmitz, Dietmar; Kneussel, Matthias.
in: NEURON, Jahrgang 70, Nr. 1, 1, 2011, S. 66-81.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Muskelin regulates actin filament- and microtubule-based GABA(A) receptor transport in neurons.
AU - Heisler, Frank
AU - Löbrich, Sven
AU - Pechmann, Yvonne
AU - Maier, Nikolaus
AU - Zivkovic, Aleksandar R
AU - Tokito, Mariko
AU - Hausrat, Torben
AU - Schweizer, Michaela
AU - Bähring, Robert
AU - Holzbaur, Erika L F
AU - Schmitz, Dietmar
AU - Kneussel, Matthias
PY - 2011
Y1 - 2011
N2 - 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 ?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.
AB - 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 ?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.
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - HEK293 Cells
KW - Neurons/metabolism
KW - Mice, 129 Strain
KW - Actin Cytoskeleton/metabolism
KW - Cell Adhesion Molecules/physiology
KW - Intracellular Signaling Peptides and Proteins/physiology
KW - Microtubules/metabolism
KW - Protein Transport/physiology
KW - Receptors, GABA-A/metabolism
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - HEK293 Cells
KW - Neurons/metabolism
KW - Mice, 129 Strain
KW - Actin Cytoskeleton/metabolism
KW - Cell Adhesion Molecules/physiology
KW - Intracellular Signaling Peptides and Proteins/physiology
KW - Microtubules/metabolism
KW - Protein Transport/physiology
KW - Receptors, GABA-A/metabolism
M3 - SCORING: Journal article
VL - 70
SP - 66
EP - 81
JO - NEURON
JF - NEURON
SN - 0896-6273
IS - 1
M1 - 1
ER -