Interaction of the amyloid precursor like protein 1 with the α2A-adrenergic receptor increases agonist-mediated inhibition of adenylate cyclase

Weber, Bernd; Schaper, C.; Scholz, Jens; Bein, Berthold; Rodde, Cornelia; Tonner, Peter H.

doi:10.1016/j.cellsig.2006.01.017

Cited by 12 publications

(11 citation statements)

References 42 publications

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“…2). The fine tuning of adrenoceptor signaling may be even more complex, as the list of receptor-associated proteins is continuously growing and includes the recent identification of an association between α 2A -receptors and amyloid precursor like protein 1 (Lefkowitz and Shenoy 2005;Weber et al 2006).…”

Section: Adrenergic Signal Transductionmentioning

confidence: 99%

Adrenoceptors and signal transduction in neurons

2006

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The adrenergic system is an essential regulator of neuronal, endocrine, cardiovascular, vegetative, and metabolic functions. The endogenous catecholamines epinephrine and norepinephrine activate G-protein-coupled receptors to transmit their signal across the plasma membrane. These adrenoceptors can be divided into three different groups: the alpha(1)-receptors (alpha(1A), alpha(1B), alpha(1D)), alpha(2)-receptors (alpha(2A), alpha(2B), alpha(2C)), and beta-receptors (beta(1), beta(2), beta(3)). This review summarizes recent findings in the field of adrenoceptor signaling in neurons and includes a discussion of receptor-associated proteins, receptor dimerization, subcellular trafficking, and fluorescence optical methods for studying the kinetics of adrenergic signaling. Spatio-temporal imaging may become an important future tool for identifying the physiological significance of these complex signaling mechanisms in vivo. Gene-targeted mouse models carrying deletions in alpha(2)-adrenoceptor have provided detailed insights into specific neuronal functions of the three alpha(2)-receptor subtypes.

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Section: Adrenergic Signal Transductionmentioning

confidence: 99%

Adrenoceptors and signal transduction in neurons

2006

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“…The C-terminal domains of all three α 2 AR subtypes also have been shown to interact with α-subunit of eukaryotic translation initiation factor 2B (eIF-2B) [34] as well as with the amyloid precursor like protein 1 (APLP1) [35], a homologue of the β-amyloid precursor protein (APP) involved in Alzheimer's disease [36]. Coexpression of APLP1 with the α 2A AR in HEK cells significantly increases α 2A AR-mediated inhibition of adenylyl cyclase activity [35]. The functional relevance of α 2 AR interactions with these proteins in native tissues has not yet been established.…”

Section: Proteins Interacting With the C-terminus Of The α 2 Armentioning

confidence: 99%

Regulation of α2AR trafficking and signaling by interacting proteins

Wang

Limbird

2007

Biochemical Pharmacology

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The continuing discovery of new G protein-coupled receptor (GPCR) interacting proteins and clarification of the functional consequences of these interactions has revealed multiple roles for these events. Some of these interactions serve to scaffold GPCRs to particular cellular micro-compartments or to tether them to defined signaling molecules, while other GPCR-protein interactions control GPCR trafficking and the kinetics of GPCR-mediated signaling transduction. This review provides a general overview of the variety of GPCR-protein interactions reported to date, and then focuses on one prototypical GPCR, the α 2 AR, and the in vitro and in vivo significance of its reciprocal interactions with arrestin and spinophilin.It seems appropriate to recognize the life and career of Arthur Hancock with a summary of studies that both affirm and surprise our preconceived notions of how nature is designed, as his career-long efforts similarly affirmed the complexity of human biology and attempted to surprise pathological changes in that biology with novel, discovery-based therapeutic interventions. Dr Hancock's love of life, of family, and of commitment to making the world a better place are a model of the life well lived, and truly missed by those who were privileged to know, and thus love, him.

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“…Previously, it has been shown that APLP1 binds to α 2A -adrenergic receptors and plays a role in regulation of α 2A -adrenergic receptor trafficking [18]. Similarly, here APLP1-mediated internalization of Ca V 2.3, may act as a negative feed-back mechanism of the channel, implicating APLP1, in such a novel regulatory role.…”

Section: Endocytosis Of Ca V 23mentioning

confidence: 99%

“…Additionally, APLP1 has been shown to interact with disabled-1 gene (Dab1), a protein involved in neuronal development and transcription initiation [17] and α 2 -adrenergic receptors [18].…”

Section: Introductionmentioning

confidence: 99%

APLP1 and Rab5A Interact with the II-III loop of the Voltage-gated Ca<sup>2+</sup>-channel Ca<sub>v</sub>2.3 and Modulate its Internalization Differently

Kanthavel¹,

Krieger²,

Dibué³

et al. 2011

Cell Physiol Biochem

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Background: Voltage gated calcium channels (VGCCs) regulate cellular activity in response to membrane depolarization by altering calcium homeostasis. Because calcium is the most versatile second messenger, regulation of the amount of VGCCs at the plasma membrane is highly critical for several essential cellular processes. Among the different types of VGCCs, the Ca_v2.3 calcium channel and its regulation mechanisms are least understood due to Ca_v2.3’s resistance to most pharmacological agents. Methods: In order to study regulation and surface expression of Ca_v2.3, a yeast two hybrid (Y2H) screen with the II-III loop of human Ca_v2.3 as bait, was performed. APLP1, a member of the APP gene family and Rab5A, an endocytotic catalyst were identified as putative interaction partners. The interaction were confirmed by immunoprecipitation. To study the functional importance of the interaction, patch-clamp recordings in Ca_v2.3 stably transfected HEK-293 cells (2C6) and surface biotin endocytosis assays were performed. Results: We are able to show that the II-III loop of the Ca_v2.3 calcium channel binds APLP1 and that this binding promotes internalization of the channel. In addition, Rab5A also binds to the same loop of the channel and exerts an inhibitory effect on APLP1 mediated channel internalization. Conclusions: This study identifies a regulation mechanism of Ca_v2.3’s surface expression, which implicates APLP1 as a regulator of calcium homeostasis. Thus APLP1 may play a crucial role in neuropathological mechanisms, which involve modulation of surface expression of voltage-gated Ca²⁺ channels.

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Interaction of the amyloid precursor like protein 1 with the α2A-adrenergic receptor increases agonist-mediated inhibition of adenylate cyclase

Cited by 12 publications

References 42 publications

Adrenoceptors and signal transduction in neurons

Adrenoceptors and signal transduction in neurons

Regulation of α2AR trafficking and signaling by interacting proteins

APLP1 and Rab5A Interact with the II-III loop of the Voltage-gated Ca<sup>2+</sup>-channel Ca<sub>v</sub>2.3 and Modulate its Internalization Differently

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