Cofilin expression induces cofilin-actin rod formation and disrupts synaptic structure and function in Aplysia synapses.
Cofilin-actin rods are inclusion-like structures that are induced by certain chemical or physical stresses in cultured cells, and the rods formed in neurons are thought to be associated with neurodegeneration. Here, we cloned an Aplysia cofilin homolog and overexpressed it in cultured neurons. Overexpressed cofilin formed rod-like structures that included actin. The overall neuronal morphology was unaffected by cofilin overexpression; however, a decrease in number of synaptic varicosities was observed. Consistent with this structural change by cofilin overexpression, the synaptic strength was reduced, and furthermore, the long-term facilitation elicited by repeated pulses of 5-hydroxytryptamine was impaired in sensory-to-motor synapses. However, cofilin overexpression did not induce programmed cell death. These findings suggest that the formation of cofilin-actin rod-like structures can lead to neurodegeneration, and this might be a mechanism of rundown of neuronal and synaptic function without cell death in neurodegenerative diseases.
Jang
Dong-Hyuk
DH
National Research Laboratory of Neurobiology, Institute of Molecular Biology and Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, San 56-1 Silim-dong Kwanak-gu, Seoul 151-742, Korea.
Han
Jin-Hee
JH
Lee
Seung-Hee
SH
Lee
Yong-Seok
YS
Park
Hyungju
H
Lee
Sue-Hyun
SH
Kim
Hyoung
H
Kaang
Bong-Kiun
BK
D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D002478:Cells, Cultured; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000209:etiology; D009474:Neurons / Q000473:pathology; D016415:Sequence Alignment; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure*; D009435:Synaptic Transmission; D014162:Transfection
D051339:Actin Depolymerizing Factors; D000199:Actins; D012701:Serotonin