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AP-1 functions primarily in retrograde trafficking, retrieving proteins from post-Golgi compartments back to TGN
"Current evidence supports a model in which AP-1 functions primarily in retrograde trafficking, retrieving proteins from post-Golgi compartments back to the TGN."
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AP-1 recruitment requires coincidence detection of Arf1-GTP and PI(4)P
"The spatial and temporal regulation of AP-1 activity depends on a sophisticated coincidence detection mechanism involving the small GTPase Arf1 (ADP-ribosylation factor 1) and the phosphoinositide PI(4)P"
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AP1B1 mutations cause KIDAR syndrome with epithelial dysfunction but preserve cognition
"Loss-of-function mutations in AP1B1 cause autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR)"
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Copper transporter mislocalization is central to KIDAR/MEDNIK pathogenesis
"Central to the pathogenesis of both KIDAR and MEDNIK syndromes is abnormal AP-1-mediated trafficking of copper transporters."
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Biallelic AP1B1 mutations cause KIDAR syndrome with epithelial abnormalities (PMID:31630788)
"Affected individuals present with a constellation of features including neonatal-onset ichthyotic erythroderma, progressive sensorineural hearing loss, photophobia with corneal involvement, failure to thrive, and thrombocytopenia."
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E-cadherin and beta-catenin mislocalization in AP1B1-deficient cells (PMID:31630788)
"E-cadherin localization shifted from tight junctional to diffuse cytoplasmic distribution, beta-catenin showed reduced membrane staining with cytoplasmic and nuclear accumulation"
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AP1B1 shows extreme evolutionary conservation with pLI score 0.99 (PMID:31630788)
"The human AP1B1 protein shares greater than 98% sequence identity with its canine ortholog, greater than 95% identity with chicken"
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Humans may express up to 12 distinct AP-1 variants depending on subunit composition (PMID:35429729)
"The combinatorial expression of these isoforms generates considerable functional diversity, with humans potentially expressing up to 12 distinct AP-1 variants depending on subunit composition"
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AP-1 mediates retrograde retrieval from endosomes to TGN (PMID:35429729)
"Studies in yeast have been particularly informative: kinetic analyses using synthetic cargo revealed that AP-1 mediates active recycling of material from late-stage TGN back to earlier stages"
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AP-1A localizes to TGN for direct basolateral pathway; AP-1B to recycling endosomes (PMID:22516199)
"AP-1A localizes predominantly to the TGN and promotes cargo exit through a direct pathway to the basolateral plasma membrane."
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Sigma1 subunit recognizes dileucine signal in ATP7B for polarized sorting (PMID:25378584)
"The sigma1 subunit of AP-1 directly recognizes a dileucine signal in ATP7B's cytoplasmic tail, and disruption of this interaction through dominant-negative sigma1 mutants causes loss of ATP7B's polarized distribution in neurons"
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mu1A knockout causes embryonic lethality at day 13.5 in mice (PMID:10811610)
"Knockout studies in mice demonstrated that targeted disruption of the mu1A-adaptin gene causes embryonic lethality at day 13.5"
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MPR46 fails to recycle from endosomes to TGN without functional AP-1 (PMID:10811610)
"MPR46 fails to recycle from endosomes back to the TGN, providing direct evidence that AP-1 is required for retrograde receptor transport"
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AP-1 has unexpected roles in apical protein localization (PMID:25387275)
"Loss of AP-1 function causes mislocalization of apical proteins and the formation of ectopic microvilli-like structures in the basolateral domain"
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Adaptin HEAT repeats classified as distinct ADB class (PMID:24975939)
"sequence analysis has classified adaptin HEAT repeats as a distinct subclass (ADB class) specific to the adaptor protein family"
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Beta subunits of AP-1 and AP-2 share 84% sequence identity (PMID:24975939)
"the beta subunits of AP-1 and AP-2 share 84% sequence identity"
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Proteomic analysis confirms AP-1 vesicles support retrograde model (PMID:38578286)
"Proteomic analysis of immunocaptured AP-1 vesicles revealed they contain TGN and endosomal proteins as well as lysosomal hydrolases, but notably very little of the anterograde adaptor GGA2, strongly supporting the retrograde trafficking model"
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Nearly 100% of AP-1 vesicles are clathrin-positive (PMID:38578286)
"Recent imaging studies confirmed that nearly 100% of AP-1 vesicles are positive for clathrin"
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PP2A dephosphorylation of beta1 enables clathrin assembly (PMID:34565296)
"Protein phosphatase 2A (PP2A)-mediated dephosphorylation of beta1 enables clathrin assembly upon membrane recruitment"
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AP-1 is exploited by SARS-CoV-2, MERS-CoV, and HIV (PMID:34565296)
"AP-1 components are exploited by viruses including SARS-CoV-2, MERS-CoV, and HIV, which selectively target the host AP-1 complex to facilitate viral entry and replication"