Conditional knockout of tumor overexpressed gene in mouse neurons affects RNA granule assembly, granule translation, LTP and short term habituation.
In neurons, specific RNAs are assembled into granules, which are translated in dendrites, however the functional consequences of granule assembly are not known. Tumor overexpressed gene (TOG) is a granule-associated protein containing multiple binding sites for heterogeneous nuclear ribonucleoprotein (hnRNP) A2, another granule component that recognizes cis-acting sequences called hnRNP A2 response elements (A2REs) present in several granule RNAs. Translation in granules is sporadic, which is believed to reflect monosomal translation, with occasional bursts, which are believed to reflect polysomal translation. In this study, TOG expression was conditionally knocked out (TOG cKO) in mouse hippocampal neurons using cre/lox technology. In TOG cKO cultured neurons granule assembly and bursty translation of activity-regulated cytoskeletal associated (ARC) mRNA, an A2RE RNA, are disrupted. In TOG cKO brain slices synaptic sensitivity and long term potentiation (LTP) are reduced. TOG cKO mice exhibit hyperactivity, perseveration and impaired short term habituation. These results suggest that in hippocampal neurons TOG is required for granule assembly, granule translation and synaptic plasticity, and affects behavior.
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut, United States of America. barbarese@nso2.uchc.edu
Elisa
E
Barbarese
Marius F
MF
Ifrim
Lawrence
L
Hsieh
Caiying
C
Guo
Vedakumar
V
Tatavarty
Michael J
MJ
Maggipinto
George
G
Korza
Jessica W
JW
Tutolo
Anthony
A
Giampetruzzi
Hien
H
Le
Xin-Ming
XM
Ma
Eric
E
Levine
Brian
B
Bishop
Duck O
DO
Kim
Shigeyuki
S
Kuwada
John H
JH
Carson
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005260:Female; D055786:Gene Knockout Techniques; D006185:Habituation, Psychophysiologic / Q000235:genetics*; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
C587430:CKAP5 protein, mouse; D008869:Microtubule-Associated Proteins; D012313:RNA