title: Preso regulation of dendritic outgrowth through PI(4,5)P2-dependent PDZ interaction with βPix.
abstract: 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 (PIP(2) ) 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 PIP(2) and it did not rescue the Preso-knockdown effect. These results indicate that PIP(2) is a key signalling molecule that regulates dendritic outgrowth through activation of small GTPase signalling via interaction between Preso and βPix.
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Mo
authors.forename: Dongmin
authors.initials: D
authors.lastname: Lee
authors.forename: Soontaek
authors.initials: S
authors.lastname: Hong
authors.forename: Seungrie
authors.initials: S
authors.lastname: Han
authors.forename: Hyojin
authors.initials: H
authors.lastname: Yeo
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.forename: Sukwoo
authors.initials: S
authors.lastname: Choi
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D020439:Growth Cones / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D054731:PDZ Domains; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D064067:Rho Guanine Nucleotide Exchange Factors
chemical_list: D000199:Actins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; C539678:FRMPD4 protein, human; C576234:FRMPD4 protein, rat; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors