transport of Staufen2-containing ribonucleoprotein complexes involves kinesin motor protein and is modulated by mitogen-activated protein kinase pathway

• Published in: Journal of neurochemistry Vol. 102; no. 6; pp. 2073 - 2084
• Main Authors: Jeong, Ji-Hye, Nam, Yeon-Ju, Kim, Seok-Yong, Kim, Eung-Gook, Jeong, Jooyoung, Kim, Hyong Kyu
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.09.2007; Blackwell Publishing Ltd; Blackwell
• Subjects: Animals; Animals, Newborn; Biochemistry; Biological and medical sciences; Ca2+/calmodulin‐dependent protein kinase II α‐subunit; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Ca²⁺/calmodulin-dependent protein kinase II α-subunit; Cell physiology; Cell receptors; Cell structures and functions; Cells, Cultured; Dendrites - metabolism; dendritic mRNA transport; Down-Regulation - physiology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Hippocampus - metabolism; Kinases; kinesin; Kinesin - antagonists & inhibitors; Kinesin - chemistry; Kinesin - metabolism; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; mitogen-activated protein kinase; Molecular and cellular biology; Neuropeptide receptors; Neurosciences; Protein Transport - physiology; Proteins; Rats; Rats, Sprague-Dawley; Ribonucleic acid; Ribonucleoproteins - metabolism; RNA; RNA, Messenger - metabolism; RNA-Binding Proteins - metabolism; Signal transduction; Sindbis viral expression; Staufen2; calmodulin-dependent protein kinase; Staufen2; Enzyme; Transferases; Biological transport; kinesin; Central nervous system; Mitogen-activated protein kinase; Subunit; Encephalon; Binding protein; Neuron; Green fluorescent protein; dendritic mRNA transport; Ca; Hippocampus; Ca2+/calmodulin-dependent protein kinase II α- subunit; Sindbis viral expression
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.04697.x

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 Ca²⁺/calmodulin-dependent protein kinase II α-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.