title: The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis.
abstract: Spine function requires precise control of the actin cytoskeleton. Kalirin-7, a GDP/GTP exchange factor for Rac1, interacts with PDZ proteins such as PSD-95, colocalizing with PSD-95 at synapses of cultured hippocampal neurons. PSD-95 and Kalirin-7 interact in vivo and in heterologous expression systems. In primary cortical neurons, transfected Kalirin-7 is targeted to spines and increases the number and size of spine-like structures. A Kalirin-7 mutant unable to interact with PDZ proteins remains in the cell soma, inducing local formation of aberrant filopodial neurites. Kalirin-7 with an inactivated GEF domain reduces the number of spines below control levels. These results provide evidence that PDZ proteins target Kalirin-7 to the PSD, where it regulates dendritic morphogenesis through Rac1 signaling to the actin cytoskeleton.
authors.affiliation: Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: P
authors.initials: P
authors.lastname: Penzes
authors.forename: R C
authors.initials: RC
authors.lastname: Johnson
authors.forename: R
authors.initials: R
authors.lastname: Sattler
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: R L
authors.initials: RL
authors.lastname: Huganir
authors.forename: V
authors.initials: V
authors.lastname: Kambampati
authors.forename: R E
authors.initials: RE
authors.lastname: Mains
authors.forename: B A
authors.initials: BA
authors.lastname: Eipper
mesh_terms: D000199:Actins / Q000378:metabolism; D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002352:Carrier Proteins; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009024:Morphogenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; C102365:Kalrn protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C033652:postsynaptic density proteins; D020830:rac1 GTP-Binding Protein