Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory
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Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory. / Hausrat, Torben J; Muhia, Mary; Gerrow, Kimberly; Thomas, Philip; Hirdes, Wiebke; Tsukita, Sachiko; Heisler, Frank F; Herich, Lena; Dubroqua, Sylvain; Breiden, Petra; Feldon, Joram; Schwarz, Juergen; Yee, Benjamin K; Smart, Trevor G; Triller, Antoine; Kneussel, Matthias.
In: NAT COMMUN, Vol. 6, 2015, p. 6872.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory
AU - Hausrat, Torben J
AU - Muhia, Mary
AU - Gerrow, Kimberly
AU - Thomas, Philip
AU - Hirdes, Wiebke
AU - Tsukita, Sachiko
AU - Heisler, Frank F
AU - Herich, Lena
AU - Dubroqua, Sylvain
AU - Breiden, Petra
AU - Feldon, Joram
AU - Schwarz, Juergen
AU - Yee, Benjamin K
AU - Smart, Trevor G
AU - Triller, Antoine
AU - Kneussel, Matthias
PY - 2015
Y1 - 2015
N2 - Neurotransmitter receptor density is a major variable in regulating synaptic strength. Receptors rapidly exchange between synapses and intracellular storage pools through endocytic recycling. In addition, lateral diffusion and confinement exchanges surface membrane receptors between synaptic and extrasynaptic sites. However, the signals that regulate this transition are currently unknown. GABAA receptors containing α5-subunits (GABAAR-α5) concentrate extrasynaptically through radixin (Rdx)-mediated anchorage at the actin cytoskeleton. Here we report a novel mechanism that regulates adjustable plasma membrane receptor pools in the control of synaptic receptor density. RhoA/ROCK signalling regulates an activity-dependent Rdx phosphorylation switch that uncouples GABAAR-α5 from its extrasynaptic anchor, thereby enriching synaptic receptor numbers. Thus, the unphosphorylated form of Rdx alters mIPSCs. Rdx gene knockout impairs reversal learning and short-term memory, and Rdx phosphorylation in wild-type mice exhibits experience-dependent changes when exposed to novel environments. Our data suggest an additional mode of synaptic plasticity, in which extrasynaptic receptor reservoirs supply synaptic GABAARs.
AB - Neurotransmitter receptor density is a major variable in regulating synaptic strength. Receptors rapidly exchange between synapses and intracellular storage pools through endocytic recycling. In addition, lateral diffusion and confinement exchanges surface membrane receptors between synaptic and extrasynaptic sites. However, the signals that regulate this transition are currently unknown. GABAA receptors containing α5-subunits (GABAAR-α5) concentrate extrasynaptically through radixin (Rdx)-mediated anchorage at the actin cytoskeleton. Here we report a novel mechanism that regulates adjustable plasma membrane receptor pools in the control of synaptic receptor density. RhoA/ROCK signalling regulates an activity-dependent Rdx phosphorylation switch that uncouples GABAAR-α5 from its extrasynaptic anchor, thereby enriching synaptic receptor numbers. Thus, the unphosphorylated form of Rdx alters mIPSCs. Rdx gene knockout impairs reversal learning and short-term memory, and Rdx phosphorylation in wild-type mice exhibits experience-dependent changes when exposed to novel environments. Our data suggest an additional mode of synaptic plasticity, in which extrasynaptic receptor reservoirs supply synaptic GABAARs.
U2 - 10.1038/ncomms7872
DO - 10.1038/ncomms7872
M3 - SCORING: Journal article
C2 - 25891999
VL - 6
SP - 6872
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
ER -