Research ExplorerPublicationsGSK3 and KIF5 regulate activity-dependent sorting of gephyri...

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, Vol. 94, No. 3-4, 24.02.2015, p. 173-8.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rathgeber, L, Gromova, KV, Schaefer, I, Breiden, P, Lohr, C & Kneussel, M 2015, 'GSK3 and KIF5 regulate activity-dependent sorting of gephyrin between axons and dendrites', EUR J CELL BIOL, vol. 94, no. 3-4, pp. 173-8. https://doi.org/10.1016/j.ejcb.2015.01.005

APA

Rathgeber, L., Gromova, K. V., Schaefer, I., Breiden, P., Lohr, C., & Kneussel, M. (2015). GSK3 and KIF5 regulate activity-dependent sorting of gephyrin between axons and dendrites. EUR J CELL BIOL, 94(3-4), 173-8. https://doi.org/10.1016/j.ejcb.2015.01.005

Vancouver

Rathgeber L, Gromova KV, Schaefer I, Breiden P, Lohr C, Kneussel M. GSK3 and KIF5 regulate activity-dependent sorting of gephyrin between axons and dendrites. EUR J CELL BIOL. 2015 Feb 24;94(3-4):173-8. https://doi.org/10.1016/j.ejcb.2015.01.005

Bibtex

@article{e54ec6e5da7e481b800fc7edc5afe66b,
title = "GSK3 and KIF5 regulate activity-dependent sorting of gephyrin between axons and dendrites",
abstract = "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.",
keywords = "Animals, Animals, Newborn, Axons, Calcium, Carrier Proteins, Cells, Cultured, Dendrites, Glycogen Synthase Kinase 3, Hippocampus, Kinesin, Membrane Proteins, Mice, Recombinant Proteins",
author = "Louisa Rathgeber and Gromova, {Kira V} and Irina Schaefer and Petra Breiden and Christian Lohr and Matthias Kneussel",
note = "Copyright {\textcopyright} 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.",
year = "2015",
month = feb,
day = "24",
doi = "10.1016/j.ejcb.2015.01.005",
language = "English",
volume = "94",
pages = "173--8",
journal = "EUR J CELL BIOL",
issn = "0171-9335",
publisher = "Urban und Fischer Verlag GmbH und Co. KG",
number = "3-4",

}

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 -