2024-03-29T04:35:29Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1242912021-12-27T16:37:57Zcom_10261_41com_10261_1col_10261_294
DIGITAL.CSIC
author
Pedraza, Neus
author
Ortiz, Raúl
author
Cornadó, Alba
author
Llobet, Artur
author
Aldea, Marti
author
Gallego, Carme
funder
Ministerio de Economía y Competitividad (España)
2015-11-02T12:17:18Z
2015-11-02T12:17:18Z
2014-10-15
Journal of Neuroscience 34(42): 13988-13997 (2014)
http://hdl.handle.net/10261/124291
10.1523/JNEUROSCI.1573-14.2014
http://dx.doi.org/10.13039/501100003329
25319695
© 2014 the authors. Local regulation of protein synthesis allows a neuron to rapidly alter the proteome in response to synaptic signals, an essential mechanism in synaptic plasticity that is altered in many neurological diseases. Synthesis of many synaptic proteins is under local control and much of this regulation occurs through structures termed RNA granules. KIS is a protein kinase that associates with stathmin, a modulator of the tubulin cytoskeleton. Furthermore, KIS is found in RNA granules and stimulates translation driven by the β-actin 3 'UTR in neurites. Here we explore the physiological and molecular mechanisms underlying the action of KIS on hippocampal synaptic plasticity in mice. KIS downregulation compromises spine development, alters actin dynamics, and reduces postsynaptic responsiveness. The absence of KIS results in a significant decrease of protein levels of PSD-95, a postsynaptic scaffolding protein, and the AMPAR subunits GluR1 and GluR2 in a CPEB3-dependent manner. Underlying its role in spine maturation, KIS is able to suppress the spine developmental defects caused by CPEB3 overexpression. Moreover, either by direct or indirect mechanisms, KIS counteracts the inhibitory activity of CPEB3 on the GluR2 3 'UTR at both mRNA translation and polyadenylation levels. Our study provides insights into the mechanisms that mediate dendritic spine morphogenesis and functional synaptic maturation, and suggests KIS as a link regulating spine cytoskeleton and postsynaptic activity in memory formation.
eng
openAccess
AMPA receptors
hippocampus
KIS
local translation
local translation
spine remodeling
synaptic plasticity
KIS, A kinase associated with microtubule regulators, Enhances translation of AMPA receptors and stimulates dendritic spine remodeling
artículo
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https://digital.csic.es/bitstream/10261/124291/4/Pedraza-Journal-Neuroscience-2014-v34-p13988.pdf
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Pedraza-Journal-Neuroscience-2014-v34-p13988.pdf.txt
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Pedraza-Journal-Neuroscience-2014-v34-p13988.pdf.txt