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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism
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Amino Acid Motifs / physiology
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Amino Acid Sequence
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Animals
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Binding Sites / physiology
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Carrier Proteins*
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / metabolism
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Dendrites / metabolism*
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Dendrites / ultrastructure
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Disks Large Homolog 4 Protein
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Female
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / metabolism*
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Hippocampus / cytology
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Hippocampus / metabolism
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Morphogenesis / physiology
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Nerve Tissue Proteins / metabolism
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Neurons / metabolism*
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Neurons / ultrastructure
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Protein Structure, Tertiary / physiology
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Rats
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Rats, Sprague-Dawley
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Synapses / metabolism
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Transfection
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Two-Hybrid System Techniques
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rac1 GTP-Binding Protein / metabolism
Substances
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Actins
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Carrier Proteins
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Guanine Nucleotide Exchange Factors
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Intracellular Signaling Peptides and Proteins
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Kalrn protein, rat
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Membrane Proteins
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Nerve Tissue Proteins
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postsynaptic density proteins
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rac1 GTP-Binding Protein