Local Control of AMPA Receptor Trafficking at the Postsynaptic Terminal by a Small GTPase of the Rab Family

Gerges, Nashaat Z.; Backos, Donald S.; Esteban, José A.

doi:10.1074/jbc.m404982200

Cited by 131 publications

(150 citation statements)

References 73 publications

(70 reference statements)

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“…4 A, scheme). As previously published (Gerges et al, 2004), overexpression of EGFP-Rab11-DN the activity-dependent delivery of GluA1-containing AMPARs from intracellular compartments into synapses during LTP (Park et al, 2004;Brown et al, 2007). To evaluate the role of Rab11 in AMPAR synaptic delivery upon cholesterol removal, we used a well-characterized dominant-negative (DN) version has no significant effect on synaptic AMPAR currents under basal conditions (Fig.…”

Section: Synaptic Potentiation Induced By Cholesterol Removal Is Medimentioning

confidence: 99%

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

Brachet¹,

Norwood²,

Brouwers³

et al. 2015

J Gen Physiol

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Section: Synaptic Potentiation Induced By Cholesterol Removal Is Medimentioning

confidence: 99%

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

Brachet¹,

Norwood²,

Brouwers³

et al. 2015

J Gen Physiol

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Section: Introductionmentioning

confidence: 99%

“…Rab8 is known to regulate traffic along the TGN-RE-plasma membrane pathway, but whether this involves traffic into, through or out from the RE is not clear. Rab8 is also involved in AMPA recruitment to dendritic spines from the RE of neurons and thus may serve in both sorting and storage functions of the RE (Huber et al, 1993a;Gerges et al, 2004).Given the diverse roles of Rab8 in a variety of contexts, it could potentially act 1) in the transport of vesicles from the TGN to the RE, perhaps controlling fusion into the RE; 2) in organizing the sorting of basolateral traffic into subdomains of the RE as vesicular traffic enters this structure; or 3) in budding from the RE and delivery of cargo to the plasma membrane, including the penetration of the actin-filament web near the plasma membrane (Peranen et al, 1996;Hattula et al, 2002). In an effort to resolve these issues, we examined the requirement for Rab8 in the polarized sorting of endocytic ligands and secreted proteins in MDCK cells.…”

mentioning

confidence: 99%

Rab8 Regulates Basolateral Secretory, But Not Recycling, Traffic at the Recycling Endosome

Henry

Sheff

2008

MBoC

109

116

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Rab8 is a monomeric GTPase that regulates the delivery of newly synthesized proteins to the basolateral surface in polarized epithelial cells. Recent publications have demonstrated that basolateral proteins interacting with the 1-B clathrin adapter subunit pass through the recycling endosome (RE) en route from the TGN to the plasma membrane. Because Rab8 interacts with these basolateral proteins, these findings raise the question of whether Rab8 acts before, at, or after the RE. We find that Rab8 overexpression during the formation of polarity in MDCK cells, disrupts polarization of the cell, explaining how Rab8 mutants can disrupt basolateral endocytic and secretory traffic. However, once cells are polarized, Rab8 mutants cause mis-sorting of newly synthesized basolateral proteins such as VSV-G to the apical surface, but do not cause mis-sorting of membrane proteins already at the cell surface or in the endocytic recycling pathway. Enzymatic ablation of the RE also prevents traffic from the TGN from reaching the RE and similarly results in mis-sorting of newly synthesized VSV-G. We conclude that Rab8 regulates biosynthetic traffic through REs to the plasma membrane, but not trafficking of endocytic cargo through the RE. The data are consistent with a model in which Rab8 functions in regulating the delivery of TGN-derived cargo to REs. INTRODUCTIONThe Rab proteins are small monomeric GTPases of the Ras family. More than 60 known Rabs collectively regulate the flow of nearly all membrane traffic within the cell (Pfeffer, 1994;Gurkan et al., 2005;Jordens et al., 2005). Of these, mammalian Rab8 has been associated with the flow of newly synthesized proteins to the basolateral surface in polarized epithelial cells (Huber et al., 1993b;Moritz et al., 2001). In yeast, the Rab8 homolog, sec4, is also required for the targeting of membrane traffic to the plasma membrane (Guo et al., 1999). It has been suggested that Rab8 may be active in delivery of secretory cargo from the TGN to the plasma membrane. (Chen et al., 1993;Huber et al., 1993b). Studies of vesicular stomatitis virus protein G (VSV-G) delivery from the trans-Golgi network (TGN) have suggested that this process is regulated by Rab8, as dominant-negative (DN) mutants of Rab8 interfere with the delivery of basolateral cargo (Huber et al., 1993b). Rab8 is not localized to the TGN; rather it is localized at or near the recycling endosome (RE) in both polarized and nonpolarized cells (Hattula et al., 2006; Roland et al., 2007). The function of Rab8 at the RE is likely to regulate recycling of membrane traffic, although its role in polarized sorting is not clear. Rab8 is not required for the delivery of all basolateral proteins, but appears to be obligatory in the case of those that bear a tyrosine-dependent basolateral-sorting determinant capable of interacting with the clathrin adapter 1-B (Ang et al., 2003). The basolateral TGN-to-plasma membrane trafficking pathway is not as direct as once thought. Recent reports demonstrate clearly that 1-B-dependent basolater...

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“…PSD-95 may also function in the anchoring of GluR1 containing AMPARs, since expression of this protein in hippocampal slice cultures upregulates the amount of GluR1 found in synapses and increases synaptic transmission, occluding LTP (Ehrlich and Malinow, 2004;Gerges et al, 2004). An enhancement of LTP is also observed in PSD-95 knockout mice (Migaud et al, 1998), and similar findings were reported in another deletion mutant of PSD-95 (Beique et al, 2006).…”

Section: Role Of Ampars In Ltpmentioning

confidence: 99%

“…Also, the mechanisms involved in the regulation of Ras activity that are relevant to its effects in the regulation of AMPAR trafficking remain unknown. Rab8 is a distinct small GTPase that is also necessary for the synaptic delivery of GluR1-containing AMPARs induced by a constitutively active form of CaMKII, overexpression of PSD-95 and induction of LTP in cultured hippocampal slices (Gerges et al, 2004). Rab8 is present in both trans-Golgi network and recycling endosomes (Ang et al, 2003), but it was proposed that the effects of this small GTPase on LTP occur at the level of the former compartment (Gerges et al, 2004).…”

Section: Role Of Ampars In Ltpmentioning

confidence: 99%

Regulation of AMPA receptors and synaptic plasticity

et al. 2009

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Local Control of AMPA Receptor Trafficking at the Postsynaptic Terminal by a Small GTPase of the Rab Family

Cited by 131 publications

References 73 publications

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

Rab8 Regulates Basolateral Secretory, But Not Recycling, Traffic at the Recycling Endosome

Regulation of AMPA receptors and synaptic plasticity

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