Dendritic mRNA targeting and translation.
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Dendritic mRNA targeting and translation. / Kindler, Stefan; Kreienkamp, Hans-Jürgen.
in: ADV EXP MED BIOL, Jahrgang 970, 2012, S. 285-305.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Dendritic mRNA targeting and translation.
AU - Kindler, Stefan
AU - Kreienkamp, Hans-Jürgen
PY - 2012
Y1 - 2012
N2 - Selective targeting of specific mRNAs into neuronal dendrites and their locally regulated translation at particular cell contact sites contribute to input-specific synaptic plasticity. Thus, individual synapses become decision-making units, which control gene expression in a spatially restricted and nucleus-independent manner. Dendritic targeting of mRNAs is achieved by active, microtubule-dependent transport. For this purpose, mRNAs are packaged into large ribonucleoprotein (RNP) particles containing an array of trans-acting RNA-binding proteins. These are attached to molecular motors, which move their RNP cargo into dendrites. A variety of proteins may be synthesized in dendrites, including signalling and scaffold proteins of the synapse and neurotransmitter receptors. In some cases, such as the alpha subunit of the calcium/calmodulin-dependent protein kinase II (?CaMKII) and the activity-regulated gene of 3.1 kb (Arg3.1, also referred to as activity-regulated cDNA, Arc), their local synthesis at synapses can modulate long-term changes in synaptic efficiency. Local dendritic translation is regulated by several signalling cascades including Akt/mTOR and Erk/MAP kinase pathways, which are triggered by synaptic activity. More recent findings show that miRNAs also play an important role in protein synthesis at synapses. Disruption of local translation control at synapses, as observed in the fragile X syndrome (FXS) and its mouse models and possibly also in autism spectrum disorders, interferes with cognitive abilities in mice and men.
AB - Selective targeting of specific mRNAs into neuronal dendrites and their locally regulated translation at particular cell contact sites contribute to input-specific synaptic plasticity. Thus, individual synapses become decision-making units, which control gene expression in a spatially restricted and nucleus-independent manner. Dendritic targeting of mRNAs is achieved by active, microtubule-dependent transport. For this purpose, mRNAs are packaged into large ribonucleoprotein (RNP) particles containing an array of trans-acting RNA-binding proteins. These are attached to molecular motors, which move their RNP cargo into dendrites. A variety of proteins may be synthesized in dendrites, including signalling and scaffold proteins of the synapse and neurotransmitter receptors. In some cases, such as the alpha subunit of the calcium/calmodulin-dependent protein kinase II (?CaMKII) and the activity-regulated gene of 3.1 kb (Arg3.1, also referred to as activity-regulated cDNA, Arc), their local synthesis at synapses can modulate long-term changes in synaptic efficiency. Local dendritic translation is regulated by several signalling cascades including Akt/mTOR and Erk/MAP kinase pathways, which are triggered by synaptic activity. More recent findings show that miRNAs also play an important role in protein synthesis at synapses. Disruption of local translation control at synapses, as observed in the fragile X syndrome (FXS) and its mouse models and possibly also in autism spectrum disorders, interferes with cognitive abilities in mice and men.
KW - Animals
KW - Humans
KW - Mice
KW - MicroRNAs/genetics/metabolism
KW - Long-Term Potentiation/physiology
KW - Protein Biosynthesis/physiology
KW - Nerve Tissue Proteins/genetics/metabolism
KW - Gene Expression Regulation/physiology
KW - Synapses/physiology
KW - Biological Transport, Active/physiology
KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/metabolism
KW - Cytoskeletal Proteins/genetics/metabolism
KW - Dendrites/genetics/metabolism
KW - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
KW - Fragile X Syndrome/genetics/metabolism/physiopathology
KW - Molecular Motor Proteins/genetics/metabolism
KW - RNA, Messenger/genetics/metabolism
KW - RNA-Binding Proteins/genetics/metabolism
KW - Receptors, Neurotransmitter/genetics/metabolism
KW - Signal Transduction/genetics
KW - TOR Serine-Threonine Kinases/genetics/metabolism
KW - Animals
KW - Humans
KW - Mice
KW - MicroRNAs/genetics/metabolism
KW - Long-Term Potentiation/physiology
KW - Protein Biosynthesis/physiology
KW - Nerve Tissue Proteins/genetics/metabolism
KW - Gene Expression Regulation/physiology
KW - Synapses/physiology
KW - Biological Transport, Active/physiology
KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/metabolism
KW - Cytoskeletal Proteins/genetics/metabolism
KW - Dendrites/genetics/metabolism
KW - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
KW - Fragile X Syndrome/genetics/metabolism/physiopathology
KW - Molecular Motor Proteins/genetics/metabolism
KW - RNA, Messenger/genetics/metabolism
KW - RNA-Binding Proteins/genetics/metabolism
KW - Receptors, Neurotransmitter/genetics/metabolism
KW - Signal Transduction/genetics
KW - TOR Serine-Threonine Kinases/genetics/metabolism
M3 - SCORING: Journal article
VL - 970
SP - 285
EP - 305
JO - ADV EXP MED BIOL
JF - ADV EXP MED BIOL
SN - 0065-2598
ER -