Preso regulation of dendritic outgrowth through PI(4,5)P2-dependent PDZ interaction with βPix

In neuronal development, dendritic outgrowth and arborization are important for the establishment of neural circuit formation. A previous study reported that PSD‐95‐interacting regulator of spine morphogenesis (Preso) formed a complex with PAK‐interacting exchange factor‐beta (βPix) via PSD‐95/Dlg/Z...

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Veröffentlicht in:The European journal of neuroscience 2012-07, Vol.36 (1), p.1960-1970
Hauptverfasser: Mo, Jiwon, Lee, Dongmin, Hong, Soontaek, Han, Seungrie, Yeo, Hyojin, Sun, Woong, Choi, Sukwoo, Kim, Hyun, Lee, Hyun Woo
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container_end_page 1970
container_issue 1
container_start_page 1960
container_title The European journal of neuroscience
container_volume 36
creator Mo, Jiwon
Lee, Dongmin
Hong, Soontaek
Han, Seungrie
Yeo, Hyojin
Sun, Woong
Choi, Sukwoo
Kim, Hyun
Lee, Hyun Woo
description In neuronal development, dendritic outgrowth and arborization are important for the establishment of neural circuit formation. A previous study reported that PSD‐95‐interacting regulator of spine morphogenesis (Preso) formed a complex with PAK‐interacting exchange factor‐beta (βPix) via PSD‐95/Dlg/ZO‐1 (PDZ) interaction. Here, we report that Preso and its binding protein, βPix, are localized in dendritic growth cones. Knockdown and dominant‐negative inhibition of Preso in cultured neurons markedly reduced the dendritic outgrowth but not branching, and led to a decrease in the intensity of βPix and F‐actin in neuronal dendritic tips. Moreover, phosphatidylinositol 4,5‐bisphosphate (PIP2) induced a conformational change in Preso toward the open PDZ domain and enhanced the interaction with βPix. In addition, the Preso band 4.1 protein, ezrin, radixin and moesin (FERM) domain mutant is unable to interact with PIP2 and it did not rescue the Preso‐knockdown effect. These results indicate that PIP2 is a key signalling molecule that regulates dendritic outgrowth through activation of small GTPase signalling via interaction between Preso and βPix. Preso (PSD‐95‐interacting regulator of spine morphogenesis) forms a complex with βPix (PAK‐interacting exchange factor beta) via PDZ interaction in dendritic growth cones and its interaction is required for neuronal dendritic development through the maintenance of F‐actin by activation of small GTPase signalling. Phosphatidyl inositol 4,5‐bisphosphate binding to FERM domain of Preso induces its conformational change toward open PDZ domain and enhances the interaction with βPix.
doi_str_mv 10.1111/j.1460-9568.2012.08124.x
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A previous study reported that PSD‐95‐interacting regulator of spine morphogenesis (Preso) formed a complex with PAK‐interacting exchange factor‐beta (βPix) via PSD‐95/Dlg/ZO‐1 (PDZ) interaction. Here, we report that Preso and its binding protein, βPix, are localized in dendritic growth cones. Knockdown and dominant‐negative inhibition of Preso in cultured neurons markedly reduced the dendritic outgrowth but not branching, and led to a decrease in the intensity of βPix and F‐actin in neuronal dendritic tips. Moreover, phosphatidylinositol 4,5‐bisphosphate (PIP2) induced a conformational change in Preso toward the open PDZ domain and enhanced the interaction with βPix. In addition, the Preso band 4.1 protein, ezrin, radixin and moesin (FERM) domain mutant is unable to interact with PIP2 and it did not rescue the Preso‐knockdown effect. These results indicate that PIP2 is a key signalling molecule that regulates dendritic outgrowth through activation of small GTPase signalling via interaction between Preso and βPix. Preso (PSD‐95‐interacting regulator of spine morphogenesis) forms a complex with βPix (PAK‐interacting exchange factor beta) via PDZ interaction in dendritic growth cones and its interaction is required for neuronal dendritic development through the maintenance of F‐actin by activation of small GTPase signalling. 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A previous study reported that PSD‐95‐interacting regulator of spine morphogenesis (Preso) formed a complex with PAK‐interacting exchange factor‐beta (βPix) via PSD‐95/Dlg/ZO‐1 (PDZ) interaction. Here, we report that Preso and its binding protein, βPix, are localized in dendritic growth cones. Knockdown and dominant‐negative inhibition of Preso in cultured neurons markedly reduced the dendritic outgrowth but not branching, and led to a decrease in the intensity of βPix and F‐actin in neuronal dendritic tips. Moreover, phosphatidylinositol 4,5‐bisphosphate (PIP2) induced a conformational change in Preso toward the open PDZ domain and enhanced the interaction with βPix. In addition, the Preso band 4.1 protein, ezrin, radixin and moesin (FERM) domain mutant is unable to interact with PIP2 and it did not rescue the Preso‐knockdown effect. These results indicate that PIP2 is a key signalling molecule that regulates dendritic outgrowth through activation of small GTPase signalling via interaction between Preso and βPix. Preso (PSD‐95‐interacting regulator of spine morphogenesis) forms a complex with βPix (PAK‐interacting exchange factor beta) via PDZ interaction in dendritic growth cones and its interaction is required for neuronal dendritic development through the maintenance of F‐actin by activation of small GTPase signalling. Phosphatidyl inositol 4,5‐bisphosphate binding to FERM domain of Preso induces its conformational change toward open PDZ domain and enhances the interaction with βPix.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22595022</pmid><doi>10.1111/j.1460-9568.2012.08124.x</doi><tpages>11</tpages></addata></record>
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identifier ISSN: 0953-816X
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subjects Actin
Actins - metabolism
Animals
Cells, Cultured
Dendrites - metabolism
dendritic growth cones
Dendritic spines
Disks Large Homolog 4 Protein
ezrin
F-actin
FERM domain
Growth cones
Growth Cones - metabolism
Guanine Nucleotide Exchange Factors - metabolism
Guanosinetriphosphatase
HEK293 Cells
hippocampal neuron
Humans
Inositol
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Membrane Proteins - metabolism
moesin
Morphogenesis
Mutation
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nervous system
Neural networks
Neurons - cytology
Neurons - metabolism
PDZ Domains
Phosphatidylinositol 4,5-diphosphate
Phosphatidylinositol 4,5-Diphosphate - metabolism
Postsynaptic density proteins
radixin
Rats
Rats, Sprague-Dawley
Rho Guanine Nucleotide Exchange Factors
RNA, Small Interfering
Spine
Zonula occludens-1 protein
title Preso regulation of dendritic outgrowth through PI(4,5)P2-dependent PDZ interaction with βPix
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