GSK3 and KIF5 regulate activity-dependent sorting of gephyrin between axons and dendrites
Standard
GSK3 and KIF5 regulate activity-dependent sorting of gephyrin between axons and dendrites. / Rathgeber, Louisa; Gromova, Kira V; Schaefer, Irina; Breiden, Petra; Lohr, Christian; Kneussel, Matthias.
in: EUR J CELL BIOL, Jahrgang 94, Nr. 3-4, 24.02.2015, S. 173-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - GSK3 and KIF5 regulate activity-dependent sorting of gephyrin between axons and dendrites
AU - Rathgeber, Louisa
AU - Gromova, Kira V
AU - Schaefer, Irina
AU - Breiden, Petra
AU - Lohr, Christian
AU - Kneussel, Matthias
N1 - Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.
PY - 2015/2/24
Y1 - 2015/2/24
N2 - The kinesin KIF5 transports neuronal cargoes into axons and dendrites. Isolated KIF5 motor domains preferentially move into axons, however KIF5 binding to GRIP1 or gephyrin drives the motor into dendrites, to deliver AMPA receptors (AMPARs) or glycine receptors (GlyRs), respectively. At postsynaptic sites, gephyrin forms a multimeric scaffold to anchor GlyRs and GABAA receptors (GABAARs) in apposition to inhibitory presynaptic terminals. Here, we report the unexpected observation that increased intracellular calcium through chronic activation of AMPARs, steers a newly synthesized gephyrin fusion protein (tomato-gephyrin) to axons and interferes with its normal delivery into dendrites of cultured neurons. Axonal gephyrin clusters were not apposed to presynaptic terminals, but colocalized with GlyRs and neuroligin-2 (NLG2). Notably, functional blockade of glycogen synthase kinase-3 (GSK3) and KIF5 normalized gephyrin missorting into the axonal compartment. In contrast, mutagenesis of gephyrin S270, a GSK3 target, did not contribute to axo-dendritic sorting. Our data are consistent with previous observations, which report regulation of kinesin motility through GSK3 activity. They suggest that GSK3 regulates the sorting of GlyR/gephyrin and NLG2 complexes in a KIF5-dependent manner.
AB - The kinesin KIF5 transports neuronal cargoes into axons and dendrites. Isolated KIF5 motor domains preferentially move into axons, however KIF5 binding to GRIP1 or gephyrin drives the motor into dendrites, to deliver AMPA receptors (AMPARs) or glycine receptors (GlyRs), respectively. At postsynaptic sites, gephyrin forms a multimeric scaffold to anchor GlyRs and GABAA receptors (GABAARs) in apposition to inhibitory presynaptic terminals. Here, we report the unexpected observation that increased intracellular calcium through chronic activation of AMPARs, steers a newly synthesized gephyrin fusion protein (tomato-gephyrin) to axons and interferes with its normal delivery into dendrites of cultured neurons. Axonal gephyrin clusters were not apposed to presynaptic terminals, but colocalized with GlyRs and neuroligin-2 (NLG2). Notably, functional blockade of glycogen synthase kinase-3 (GSK3) and KIF5 normalized gephyrin missorting into the axonal compartment. In contrast, mutagenesis of gephyrin S270, a GSK3 target, did not contribute to axo-dendritic sorting. Our data are consistent with previous observations, which report regulation of kinesin motility through GSK3 activity. They suggest that GSK3 regulates the sorting of GlyR/gephyrin and NLG2 complexes in a KIF5-dependent manner.
KW - Animals
KW - Animals, Newborn
KW - Axons
KW - Calcium
KW - Carrier Proteins
KW - Cells, Cultured
KW - Dendrites
KW - Glycogen Synthase Kinase 3
KW - Hippocampus
KW - Kinesin
KW - Membrane Proteins
KW - Mice
KW - Recombinant Proteins
U2 - 10.1016/j.ejcb.2015.01.005
DO - 10.1016/j.ejcb.2015.01.005
M3 - SCORING: Journal article
C2 - 25701174
VL - 94
SP - 173
EP - 178
JO - EUR J CELL BIOL
JF - EUR J CELL BIOL
SN - 0171-9335
IS - 3-4
ER -