Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
The role of the Amyloid Precursor Protein (APP) in the pathology of Alzheimer's disease (AD) has been well studied. However, the normal function of APP in the nervous system is poorly understood. Here, we characterized the role of the Drosophila homolog (APPL) in the adult giant fiber (GF) neurons. We find that endogenous APPL is transported from the synapse to the soma in the adult. Live-imaging revealed that retrograde moving APPL vesicles co-traffic with L1-type cell adhesion molecule Neuroglian (Nrg). In APPL null mutants, stationary Nrg vesicles were increased along the axon, and the number of Nrg vesicles moving in retrograde but not anterograde direction was reduced. In contrast, trafficking of endo-lysosomal vesicles, which did not co-localize with APPL in GF axons, was not affected. This suggests that APPL loss of function does not generally disrupt axonal transport but that APPL has a selective role in the effectiveness of retrograde transport of proteins it co-traffics with. While the GF terminals of APPL loss of function animals exhibited pruning defects, APPL gain of function had no disruptive effect on GF morphology and function, or on retrograde axonal transport of Nrg. However, cell-autonomous developmental expression of a secretion-deficient form of APPL (APPL-SD), lacking the α-, β-, and, γ-secretase cleavage sites, resulted in progressive retraction of the GF terminals. Conditional expression of APPL-SD in mature GFs caused accumulation of Nrg in normal sized synaptic terminals, which was associated with severely reduced retrograde flux of Nrg labeled vesicles in the axons. Albeit β-secretase null mutants developed GF terminals they also exhibited Nrg accumulations. This suggests that cleavage defective APPL has a toxic effect on retrograde trafficking and that β-secretase cleavage has a function in Nrg sorting in endosomal compartments at the synapse. In summary, our results suggest a role for APPL and its proteolytic cleavage sites in retrograde trafficking, thus our findings are of relevance to the understanding of the endogenous role of APP as well as to the development of therapeutic treatments of Alzheimer's disease.
Pubmed ID: 31354437
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Commercial organization for research and development genomics services and technical support to researchers.
View all literature mentionsWe provide high quality Drosophila transgenic service to both research institutions and companies. We offer you partial to full service ranging from DNA preparation, embryo microinjection, screening for white+, yellow+, and/or GFP/RFP phenotypes, to balancing crosses. Most importantly, the cost of our Drosophila embryo injection services is more reasonable compared to that of others. With a large number of facilities and the highly experienced staff, we are able to initiate the process immediately upon receiving your sample. Our friendly web-based database allows you to track your sample status, service history and more.
View all literature mentionsServes Drosophila research community by collecting and distributing DNA clones and vectors; collecting and distributing Drosophila cell lines; developing and testing genomics technologies for use in Drosophila and assisting members of the research community in their use.
View all literature mentionsCollects, maintains and distributes Drosophila melanogaster strains for research. Emphasis is placed on genetic tools that are useful to a broad range of investigations. These include basic stocks of flies used in genetic analysis such as marker, balancer, mapping, and transposon-tagging strains; mutant alleles of identified genes, including a large set of transposable element insertion alleles; defined sets of deficiencies and a variety of other chromosomal aberrations; engineered lines for somatic and germline clonal analysis; GAL4 and UAS lines for targeted gene expression; enhancer trap and lacZ-reporter strains with defined expression patterns for marking tissues; and a collection of transposon-induced lethal mutations.
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis unknown targets Mouse IgM,
View all literature mentionsThis monoclonal targets APPL (d-300)
View all literature mentionsThis monoclonal targets V5 Tag
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis monoclonal targets Mouse Drosophila neuroglian
View all literature mentionsThis unknown targets Mouse IgM,
View all literature mentionsThis polyclonal secondary targets IgY (H+L)
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Appl.V5}3; MKRS/TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Appl.sdDeltaCg}KW from BDSC.
View all literature mentionsMicroscope imaging software suite used with Nikon products. NIS-Elements includes software applications for advanced and standard research, documentation, confocal microscopy, and high-content analysis.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-GFP-LAMP}2; P{w[+m*]=nSyb-GAL4.S}3/T(2;3)TSTL, CyO: TM6B, Tb[1] from BDSC.
View all literature mentionsVector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR68A06-GAL4}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=R17A04-p65.AD}attP40; P{y[+t7.7] w[+mC]=R68A06-GAL4.DBD}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR68A06-GAL4}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Appl.V5}3; MKRS/TM6B, Tb[1] from BDSC.
View all literature mentionsThis unknown targets Mouse IgM,
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Appl.T}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-Appl.sd}2 from BDSC.
View all literature mentionsSoftware suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-Dcr-2.D}2 from BDSC.
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Appl.T}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name Appl[d] w[*] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR91H05-GAL4}attP2 from BDSC.
View all literature mentionsThis monoclonal targets Mouse Drosophila neuroglian
View all literature mentionsVector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
View all literature mentionsSoftware suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.
View all literature mentionsThis monoclonal targets V5 Tag
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-Appl.sdDeltaNPTY}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-GFP-LAMP}2; P{w[+m*]=nSyb-GAL4.S}3/T(2;3)TSTL, CyO: TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118] from BDSC.
View all literature mentionsVector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-Appl.sd}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-Dcr-2.D}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=R17A04-p65.AD}attP40; P{y[+t7.7] w[+mC]=R68A06-GAL4.DBD}attP2 from BDSC.
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis monoclonal targets APPL (d-300)
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Appl.sdDeltaCg}KW from BDSC.
View all literature mentionsMicroscope imaging software suite used with Nikon products. NIS-Elements includes software applications for advanced and standard research, documentation, confocal microscopy, and high-content analysis.
View all literature mentionsThis unknown targets Mouse IgM,
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-Appl.sdDeltaNPTY}3 from BDSC.
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR91H05-GAL4}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01457}attP2 from BDSC.
View all literature mentionsThis polyclonal secondary targets IgY (H+L)
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01457}attP2 from BDSC.
View all literature mentions