The transport of Staufen2-containing ribonucleoprotein complexes involves kinesin motor protein and is modulated by mitogen-activated protein kinase pathway.
There is increasing evidence showing that mRNA is transported to the neuronal dendrites in ribonucleoprotein (RNP) complexes or RNA granules, which are aggregates of mRNA, rRNA, ribosomal proteins, and RNA-binding proteins. In these RNP complexes, Staufen, a double-stranded RNA-binding protein, is believed to be a core component that plays a key role in the dendritic mRNA transport. This study investigated the molecular mechanisms of the dendritic mRNA transport using green fluorescent protein-tagged Staufen2 produced employing a Sindbis viral expression system. The kinesin heavy chain was found to be associated with Staufen2. The inhibition of kinesin resulted in a significant decrease in the level of dendritic transport of the Staufen2-containing RNP complexes in neurons under non-stimulating or stimulating conditions. This suggests that the dendritic transport of the Staufen2-containing RNP complexes use kinesin as a motor protein. A mitogen-activated protein kinase inhibitor, PD98059, inhibited the activity-induced increase in the amount of both the Staufen2-containing RNP complexes and Ca(2+)/calmodulin-dependent protein kinase II alpha-subunit mRNA in the distal dendrites of cultured hippocampal neurons. Overall, these results suggest that dendritic mRNA transport is mediated via the Staufen2 and kinesin motor proteins and might be modulated by the neuronal activity and mitogen-activated protein kinase pathway.
Jeong
Ji-Hye
JH
Department of Medicine and Microbiology, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, KoreaDepartment of Medicine and Biochemistry, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
Nam
Yeon-Ju
YJ
Department of Medicine and Microbiology, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, KoreaDepartment of Medicine and Biochemistry, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
Kim
Seok-Yong
SY
Department of Medicine and Microbiology, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, KoreaDepartment of Medicine and Biochemistry, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
Kim
Eung-Gook
EG
Department of Medicine and Microbiology, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, KoreaDepartment of Medicine and Biochemistry, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
Jeong
Jooyoung
J
Department of Medicine and Microbiology, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, KoreaDepartment of Medicine and Biochemistry, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
Kim
Hyong Kyu
HK
Department of Medicine and Microbiology, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, KoreaDepartment of Medicine and Biochemistry, Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
D000818:Animals; D000831:Animals, Newborn; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D021381:Protein Transport / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012261:Ribonucleoproteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C492188:Stau2 protein, rat; D049452:Green Fluorescent Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517675:Camk2a protein, rat; D016547:Kinesins