beta-adducin (Add2) KO mice show synaptic plasticity, motor coordination and behavioral deficits accompanied by changes in the expression and phosphorylation levels of the alpha- and gamma-adducin subunits.
Adducins are a family of proteins found in cytoskeleton junctional complexes, which bind and regulate actin filaments and actin-spectrin complexes. In brain, adducin is expressed at high levels and is identified as a constituent of synaptic structures, such as dendritic spines and growth cones of neurons. Adducin-induced changes in dendritic spines are involved in activity-dependent synaptic plasticity processes associated with learning and memory, but the mechanisms underlying these functions remain to be elucidated. Here, beta-adducin knockout (KO) mice were used to obtain a deeper insight into the role of adducin in these processes. We showed that beta-adducin KO mice showed behavioral, motor coordination and learning deficits together with an altered expression and/or phosphorylation levels of alpha-adducin and gamma-adducin. We found that beta-adducin KO mice exhibited deficits in learning and motor performances associated with an impairment of long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus. These effects were accompanied by a decrease in phosphorylation of adducin, a reduction in alpha-adducin expression levels and upregulation of gamma-adducin in hippocampus, cerebellum and neocortex of mutant mice. In addition, we found that the mRNA encoding beta-adducin is also located in dendrites, where it may participate in the fine modulation of LTP and LTD. These results strongly suggest coordinated expression and phosphorylation of adducin subunits as a key mechanism underlying synaptic plasticity, motor coordination performance and learning behaviors.
Porro
F
F
ICGEB, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Rosato-Siri
M
M
Leone
E
E
Costessi
L
L
Iaconcig
A
A
Tongiorgi
E
E
Muro
A F
AF
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002148:Calmodulin-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000502:physiology; D007859:Learning Disabilities / Q000209:etiology; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D001523:Mental Disorders / Q000209:etiology; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology*; D019957:Motor Skills Disorders / Q000209:etiology; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D012333:RNA, Messenger; D000099291:Adducins