2013
DOI: 10.1074/jbc.m113.480079
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Abstract: Background: Axonal transport of BACE1 and the regulation of BACE1 synaptic localization remain to be fully characterized. Results: Colocalization of BACE1 with synaptophysin was reduced by overexpression of RTN3. This reduction was due to reduced BACE1 axonal transport. Conclusion: Increased interaction of RTN3 with BACE1 in the soma impacts axonal transport of BACE1. Significance: Changes of BACE1 synaptic localization potentially alter synaptic A␤ generation and amyloid deposition.

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Cited by 41 publications
(35 citation statements)
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References 64 publications
(38 reference statements)
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“…BACE1 is concentrated in neuronal presynaptic terminals, 32,33 suggesting an important role for BACE1 at the synapse. Consistent with BACE1 neuronal localisation, recent studies of BACE1 −/− mice have shown complex neurological phenotypes, including axon guidance defects, 3436 hypomyelination, 3739 memory deficits, 19,28,30,40,41 muscle spindle reduction, 42 neurochemical deficits, 43 neurogenesis and astrogenesis abnormalities, 44 neurodegeneration with age, 45 spine density reduction, 46 retinal pathology, 47 schizophrenia endophenotypes, 46 and seizures, 40,45,48 among other phenotypes (table 1).…”
Section: Bace Physiological Functionsmentioning
confidence: 99%
“…BACE1 is concentrated in neuronal presynaptic terminals, 32,33 suggesting an important role for BACE1 at the synapse. Consistent with BACE1 neuronal localisation, recent studies of BACE1 −/− mice have shown complex neurological phenotypes, including axon guidance defects, 3436 hypomyelination, 3739 memory deficits, 19,28,30,40,41 muscle spindle reduction, 42 neurochemical deficits, 43 neurogenesis and astrogenesis abnormalities, 44 neurodegeneration with age, 45 spine density reduction, 46 retinal pathology, 47 schizophrenia endophenotypes, 46 and seizures, 40,45,48 among other phenotypes (table 1).…”
Section: Bace Physiological Functionsmentioning
confidence: 99%
“…et al, 2012), RTN3 (Deng et al, 2013), Rab11 and Eps15 homology domain proteins (Buggia-Prevot et al, 2013, 2014; Udayar et al, 2013). The enhanced localization of BACE1 at synaptic sites is suggested to increase release of Aβ by the synaptic terminals and directly facilitates amyloid deposition in AD patients (Sadleir et al, 2016).…”
Section: Cellular Trafficking Of Bace1mentioning
confidence: 99%
“…Altering trafficking of BACE1 in secretory compartments is therefore another strategy to reduce or enhance BACE1 activity (Jiang et al, 2014; Tan and Evin, 2012; Vassar et al, 2014). For instance, enhanced retention of BACE1 by an ER protein such as RTN/Nogo in the ER can significantly reduce BACE1 cleavage of APP, thereby decreasing Aβ production (Araki et al, 2012; Deng et al, 2013; He et al, 2004; Shi et al, 2014; Shi et al, 2009; Shi et al, 2013; Wojcik et al, 2007). Increased trafficking of BACE1 in the more acidic endosomes by cellular trafficking proteins such as a Vps10p domain-sorting receptor sortilin (Finan et al, 2011), the small GTPase ADP ribosylation factor 6 (ARF6) (Sannerud et al, 2011), Rab-GTPases Rab11 (Udayar et al, 2013), and Sorting nexin 12 (Zhao et al, 2012) results in significant increases in Aβ generation.…”
Section: Brief Overview Of Bace1mentioning
confidence: 99%
“…Depletion of both GGA1 and GGA3 induces a rapid and robust elevation of BACE1, and such an effect will likely be interfered with by flotillin, which can compete with GGA proteins for binding to the same dileucine motif in the BACE1 tail (John et al, 2014). In neurons, BACE1 is targeted to both axons and dendrites, and its preferential transport to the axonal terminus versus somatodendrites can be regulated by altered levels of calsyntenin-1 (Steuble et al, 2012; Vagnoni et al, 2012), retromer vps35 (Wang et al, 2012a; Wen et al, 2011), RTN3 (Deng et al, 2013), Rab11, and Eps15 homology domain proteins (Buggia-Prevot et al, 2014; Buggia-Prevot et al, 2013; Udayar et al, 2013). The localization of BACE1 in synaptic sites can impact the processing of its substrates.…”
Section: Brief Overview Of Bace1mentioning
confidence: 99%