Journal of Biological Chemistry · 2004 · 148 citations · 61 references
Life SciencesNeurobiologyNeuroscienceIntracellular TransportMolecular NeuroscienceSynaptic PlasticityNeurotransmissionNeurotransmitter ReceptorsProtein TraffickingProtein Trafficking In NeuronsSynaptic TransmissionVesicle TraffickingAmpa ReceptorsGlutamate Receptor TraffickingGlutamatergic SynapsesIntracellular Vesicle TransportProtein Trafficking At SynapsesRab Gtpase-mediated TraffickingRab Gtpase-mediated Vesicle TraffickingTrans-golgi Transport
The delivery of neurotransmitter receptors into the synaptic membrane is essential for synaptic function and plasticity. However, the molecular mechanisms of these specialized trafficking events and their integration with the intracellular membrane transport machinery are virtually unknown. Here, we have investigated the role of the Rab family of membrane sorting proteins in the late stages of receptor trafficking into the postsynaptic membrane. We have identified Rab8, a vesicular transport protein associated with trans-Golgi network membranes, as a critical component of the cellular machinery that delivers AMPA-type glutamatergic receptors (AMPARs) into synapses. Using electron microscopic techniques, we have found that is in the synaptic the postsynaptic that is for the synaptic delivery of and receptor is for delivery into the for receptor transport the into the for delivery into the the delivery of into synapses. a role for the cellular machinery in the of synaptic function and the postsynaptic membrane. The delivery of neurotransmitter receptors into the synaptic membrane is essential for synaptic function and plasticity. However, the molecular mechanisms of these specialized trafficking events and their integration with the intracellular membrane transport machinery are virtually unknown. Here, we have investigated the role of the Rab family of membrane sorting proteins in the late stages of receptor trafficking into the postsynaptic membrane. We have identified Rab8, a vesicular transport protein associated with trans-Golgi network membranes, as a critical component of the cellular machinery that delivers AMPA-type glutamatergic receptors (AMPARs) into synapses. Using electron microscopic techniques, we have found that is in the synaptic the postsynaptic that is for the synaptic delivery of and receptor is for delivery into the for receptor transport the into the for delivery into the the delivery of into synapses. a role for the cellular machinery in the of synaptic function and the postsynaptic membrane. is critical for the and of in the and is of as the cellular for and synaptic and is the and delivery of neurotransmitter receptors into synapses. However, is of the that neurotransmitter receptors into the postsynaptic membrane. these specialized trafficking events are with the intracellular membrane transport of membrane trafficking the neurotransmitter the in and AMPA-type glutamatergic receptors (AMPARs) AMPA-type glutamatergic protein AMPA-type glutamatergic protein are of synapses. in and of the synaptic membrane in and trafficking is synaptic and in are of of receptor are in receptor receptor synaptic and in and of in a of synaptic and trafficking have as and However, the cellular and molecular mechanisms membrane transport in these are of the Rab family of are of intracellular membrane sorting in are membrane transport Rab proteins are for function in Rab protein in is a of family the of neurotransmitter with the membrane and of synaptic the role of Rab proteins in neurotransmitter receptor and synaptic function the postsynaptic of the Rab family are in delivery into the Rab8, and and the transport of trans-Golgi into of the membrane. is in the into the membrane transport late and trans-Golgi network Rab proteins late stages of the trafficking into the membrane and are receptor into the postsynaptic we have the role of these Rab proteins in synaptic function and in in the late trafficking events that into synapses. 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However, is of the that neurotransmitter receptors into the postsynaptic membrane. these specialized trafficking events are with the intracellular membrane transport of membrane trafficking the neurotransmitter the in and The AMPA-type glutamatergic receptors (AMPARs) AMPA-type glutamatergic protein AMPA-type glutamatergic protein are of synapses. in and of the synaptic membrane in and trafficking is synaptic and in are of of receptor are in receptor receptor synaptic and in and of in a of synaptic and trafficking have as and However, the cellular and molecular mechanisms membrane transport in these are unknown. of the Rab family of are of intracellular membrane sorting in are membrane transport Rab proteins are for function in Rab protein in is a of family the of neurotransmitter with the membrane and of synaptic the role of Rab proteins in neurotransmitter receptor and synaptic function the postsynaptic of the Rab family are in delivery into the Rab8, and and the transport of trans-Golgi into of the membrane. is in the into the membrane transport late and trans-Golgi network Rab proteins late stages of the trafficking into the membrane and are receptor into the postsynaptic membrane. we have the role of these Rab proteins in synaptic function and in in the late trafficking events that into synapses. 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transport of membrane proteins into of postsynaptic of electron found the postsynaptic the postsynaptic in are with of of the found with for the The of the found found the postsynaptic as as of the is the of the in is in and as as in in with in the and these of that the protein membrane in for the of in that in the of membrane proteins the into is that with transport into We and delivery and for the in The of the receptor in is the of and is the of the in the of into the and the for for a of receptor delivery and with the intracellular of that transport into with a trafficking the synaptic delivery of the for into the is in a of we the delivery of and the we the with a protein the of the of with and receptor delivery into a of with as the with the of receptor the the and the of the as of the and the for and as the the in the and the are their with their The of are in in and in the as with the for for that the delivery of the of the the of receptor in the with the receptor for for the 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Using we that is for the delivery of into the for transport of the into the for delivery into the membrane. the synaptic of and we that is for the of and their synaptic as we that the transport of intracellular membrane in the the synaptic is a of transport the trans-Golgi network into the membrane. is in the delivery of a of membrane proteins in However, of the is that the of into the specialized that the postsynaptic membrane. of role of in the synaptic delivery of Rab8, in the is in the the postsynaptic is for the synaptic of the molecular of are the of that in the that of function of the transport of in receptor delivery into the is in with a that for the transport of a we the for is that a role in membrane trafficking in as in as with the in is with the role of in and are transport the trans-Golgi that intracellular the trans-Golgi network with these and that are trans-Golgi network into a delivery of membrane proteins the trans-Golgi network into the membrane is in trans-Golgi network and and a role of in membrane sorting we have found that the of receptors and the delivery of we these of receptors are intracellular a is the for of However, membrane and that and receptors have we that the synaptic delivery of receptors synaptic is the trans-Golgi the of receptors a specialized in the is that in the of synaptic is these Rab proteins are the trafficking of of the that synaptic delivery a specialized membrane is a role for in of that that the membrane with However, that is the Rab family that the late stages of membrane transport that in the synaptic delivery of receptor and delivery these of the cellular the Rab machinery in and the membrane trafficking events that the of the postsynaptic The Rab family of is intracellular membrane trafficking in in However, is that have the role of Rab proteins in membrane is essential and postsynaptic The is is neurotransmitter and the the mechanisms are We have the role of the Rab Rab8, and the postsynaptic have identified as a critical in postsynaptic membrane trafficking and plasticity. membrane trafficking and a the of in stages of the have a role in synaptic we have that is a of the delivery of into synapses. 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