2009
DOI: 10.1074/jbc.m807055200
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Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Abstract: NHE5 is a brain-enriched Na ؉ /H؉ exchanger that dynamically shuttles between the plasma membrane and recycling endosomes, serving as a mechanism that acutely controls the local pH environment. In the current study we show that secretory carrier membrane proteins (SCAMPs), a group of tetraspanning integral membrane proteins that reside in multiple secretory and endocytic organelles, bind to NHE5 and co-localize predominantly in the recycling endosomes. In vitro protein-protein interaction assays revealed that … Show more

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Cited by 30 publications
(18 citation statements)
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“…Additional evidence for the specificity of SCAMP2 action on NKCC2 stems from the observation that SCAMP2 did not influence the distribution of Rab11 and internalized transferrin. Moreover, the specificity of SCAMP2-induced down-regulation of NKCC2 surface expression is also supported by a previous report demonstrating that NHE-5 interaction with overexpressed SCAMP2 in recycling endosomes promotes the cell surface targeting of the exchanger protein (59). Taken together, these findings suggest strongly that SCAMP2 specifically regulates NKCC2 transit through recycling endosomes to inhibit its cell surface targeting.…”
Section: Discussionsupporting
confidence: 75%
“…Additional evidence for the specificity of SCAMP2 action on NKCC2 stems from the observation that SCAMP2 did not influence the distribution of Rab11 and internalized transferrin. Moreover, the specificity of SCAMP2-induced down-regulation of NKCC2 surface expression is also supported by a previous report demonstrating that NHE-5 interaction with overexpressed SCAMP2 in recycling endosomes promotes the cell surface targeting of the exchanger protein (59). Taken together, these findings suggest strongly that SCAMP2 specifically regulates NKCC2 transit through recycling endosomes to inhibit its cell surface targeting.…”
Section: Discussionsupporting
confidence: 75%
“…It is known that Rab11 regulates trafficking of a variety of other critical proteins and cholesterol, so that other Rab11 effects might be involved. Brain proteins that are known Rab11-dependent cargos include transferrin receptor (iron uptake), brain-enriched Na ϩ /H ϩ exchanger NHE5 (cell volume and pH maintenance) (Diering et al, 2009), glycine transporter GLYT2 (glycine uptake) (Nú ñez et al, 2009), glucose transporter 1 (glucose uptake) (Wieman et al, 2007), and AMPA receptor (long-term potentiation) (Park et al, 2004). The presence of Rab11Q70L in HD neurons may also improve functions related to these proteins.…”
Section: Discussionmentioning
confidence: 99%
“…It is possible that Ral inhibition contributes to the AKT-inhibition-induced perturbation of NHE1 exocytosis and membrane localization. Further, membrane translocation of another NHE isoform, NHE5, is regulated by SCAMP2 in an Arf6-dependent manner (Diering et al, 2009). As Arf6 is also regulated by AKT signaling, via Grp1 (Li et al, 2012), it would also be relevant to address the possible role of this pathway in PDGF-aa-mediated NHE1 translocation.…”
Section: Discussionmentioning
confidence: 99%