p21-Activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties.Comments  Comment in: Mol Cell Biol. 2011 Feb;31(3):386-7; PMID: 21115726

Huang W; Zhou Z; Asrar SHenkelman MXie WJia Z

首页> 外文期刊>Molecular and Cellular Biology >p21-Activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties.Comments Comment in: Mol Cell Biol. 2011 Feb;31(3):386-7; PMID: 21115726

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p21-Activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties.Comments Comment in: Mol Cell Biol. 2011 Feb;31(3):386-7; PMID: 21115726

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The molecular mechanisms that coordinate postnatal brain enlargement, synaptic properties, and cognition remain an enigma. Here, we demonstrate that neuronal complexity controlled by p21-activated kinases (PAKs) is a key determinant for postnatal brain enlargement and synaptic properties. We showed that double-knockout (DK) mice lacking both PAK1 and PAK3 were born healthy, with normal brain size and structure, but severely impaired in postnatal brain growth, resulting in a dramatic reduction in brain volume. Remarkably, the reduced brain size was accompanied by minimal changes in total cell count, due to a significant increase in cell density. However, the DK neurons have smaller soma, markedly simplified dendritic arbors/axons, and reduced synapse density. Surprisingly, the DK mice had elevated basal synaptic responses due to enhanced individual synaptic potency but were severely impaired in bidirectional synaptic plasticity. The actions of PAK1 and PAK3 are possibly mediated by cofilin-dependent actin regulation, because the activity of cofilin and the properties of actin filaments were altered in the DK mice. These results reveal an essential in vivo role of PAK1 and PAK3 in coordinating neuronal complexity and synaptic properties and highlight the critical importance of dendrite/axon growth in dictating postnatal brain growth and attainment of normal brain size and function.

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《Molecular and Cellular Biology》 |2011年第3期|388-403|共16页
作者
Huang W; Zhou Z; Asrar SHenkelman MXie WJia Z;
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作者单位

Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, 2 Sipailou Road, Nanjing 210096, China;

Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8;

Department of Medical Biophysics, University of Toronto, Toronto, Canada;

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正文语种英语
中图分类分子生物学;
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Actin Depolymerizing Factors; Actins; Animals; Newborn; Anxiety; Axons; Behavior; Animal; Brain; Cell Count; Dendritic Spines; Hyperkinesis; Memory; Mice; Neuroglia; Neuronal Plasticity; Neurons; Organ Size; Synapses; Synaptic Transmission; p21-Activated Kinases;

p21-Activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties.Comments Comment in: Mol Cell Biol. 2011 Feb;31(3):386-7; PMID: 21115726

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