Kalirin, a multifunctional Rho guanine nucleotide exchange factor, is necessary for maintenance of hippocampal pyramidal neuron dendrites and dendritic spines.
The structures of dendritic spines and the dendritic tree, key determinants of neuronal function, are regulated by diverse inputs that affect many scaffolding and signaling molecules. Nevertheless, here we show that reduced expression of a single gene results in loss of dendritic spines and a decrease in dendritic complexity. Kalirin, a dual Rho GDP-GTP exchange factor, causes spine formation when overexpressed. Reduced expression of Kalirin in CA1 hippocampal neurons resulted in a reduction in linear spine density, with dispersion of postsynaptic density markers and elimination of presynaptic endings. Simplification of the apical dendritic tree preceded simplification of basal dendrites. Pyramidal cell axons were not dramatically altered. Although many factors determine dendrite shape and spine formation, expression of Kalirin is necessary for the normal function of these many regulatory elements.
Ma
Xin-Ming
XM
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030-3401, USA.
Huang
Jianping
J
Wang
Yanping
Y
Eipper
Betty A
BA
Mains
Richard E
RE
D000818:Animals; D019470:Biolistics; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D022081:Cell Surface Extensions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016372:RNA, Antisense / Q000096:biosynthesis / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; C102365:Kalrn protein, rat; D020033:Protein Isoforms; D016372:RNA, Antisense