| 2007 |
UNC-46 (LAMP5 ortholog in C. elegans) is a sorting factor required for localizing the vesicular GABA transporter (VGAT/UNC-47) to synaptic vesicles. In unc-46 mutants, the transporter is diffusely spread along the axon rather than concentrated at synaptic vesicles, severely reducing miniature current frequency without affecting amplitude. The vesicular GABA transporter recruits UNC-46 to synaptic vesicle precursors in the cell body, and UNC-46 in turn sorts the transporter at the cell body and during endocytosis at the synapse. |
Genetic mutant analysis in C. elegans, electrophysiology (miniature current recordings), fluorescence imaging of transporter localization |
Nature neuroscience |
High |
17558401
|
| 2007 |
BAD-LAMP (LAMP5) defines a novel early endocytic compartment in specific subtypes of cortical projection neurons. The protein is endocytosed but not found in classical lysosomal/endosomal compartments. Addition of GFP to BAD-LAMP revealed a cryptic lysosomal retention motif, suggesting the cytoplasmic tail is actively sorted away from lysosomes. In transfected HeLa cells, BAD-LAMP recycles to the plasma membrane through a dynamin/AP2-dependent mechanism. |
Subcellular fractionation, live-cell imaging, GFP-tagging, endocytosis assay in HeLa cells, immunofluorescence in primary neurons |
Journal of cell science |
Medium |
17215451
|
| 2011 |
BAD-LAMP (LAMP5) is localized in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) of freshly isolated human plasmacytoid dendritic cells (pDCs) and is rapidly lost upon activation by CpG oligonucleotides (TLR9 ligand). Expression is restricted to neurons in mice but additionally present in human pDCs. |
Immunofluorescence, subcellular fractionation, flow cytometry of isolated pDCs |
Blood |
Medium |
21642595
|
| 2016 |
In the mouse brain, LAMP5 is expressed in subpopulations of GABAergic forebrain neurons and is present at synaptic terminals overlapping with the mammalian vesicular GABA transporter (VGAT). In LAMP5-deficient mice, VGAT localization is unaffected (no conserved role in VGAT trafficking), but electrophysiological analyses reveal alterations in short-term synaptic plasticity, indicating LAMP5 controls the dynamics of evoked GABAergic transmission. Behavioral deficits include decreased anxiety and impaired olfactory discrimination. |
LAMP5 knockout mouse, immunofluorescence, electrophysiology (short-term synaptic plasticity), behavioral assays |
PloS one |
High |
27272053
|
| 2017 |
BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1+ late endosomes in human pDCs, leading to NF-κB activation and TNF production upon DNA sensing. An inducible VAMP3+/LAMP2+/LAMP1- endolysosomal compartment exists in pDCs from which TLR9 activation triggers type I interferon expression. BAD-LAMP silencing enhances TLR9 retention in this interferon-signaling compartment and amplifies downstream IFN signaling. Conversely, sustained BAD-LAMP expression promotes TLR9 sorting to late endosomes, limiting type I interferon production. TGF-β-positive microenvironments exploit this mechanism to suppress pDC IFN responses. |
siRNA silencing, immunofluorescence co-localization, endosomal fractionation, cytokine measurements (ELISA/FACS), TLR9 trafficking assays in primary human pDCs |
Nature communications |
High |
29030552
|
| 2019 |
LAMP5 functions as a novel autophagic suppressor in MLL leukemia cells, protecting MLL fusion oncoproteins from autophagic degradation. LAMP5 is a direct transcriptional target of the H3K79 histone methyltransferase DOT1L. Knockdown of LAMP5 promotes selective autophagic degradation of MLL fusion proteins and inhibits leukemia progression in animal models and primary cells. |
shRNA knockdown, in vitro and in vivo leukemia models, autophagy assays (LC3, autophagic flux), ChIP (DOT1L/H3K79me2 at LAMP5 locus), western blotting, xenograft mouse models |
Clinical cancer research |
High |
30651276
|
| 2019 |
In the mouse brainstem and spinal cord, LAMP5 is localized exclusively in inhibitory synaptic terminals. In LAMP5 knockout mice, VIAAT localization is unaltered in the lateral superior olive and ventral cochlear nuclei (no conserved role in VIAAT trafficking). LAMP5 deficiency causes increased startle response and larger auditory brainstem response wave amplitudes, indicating LAMP5 plays a role in sensorimotor processing. |
LAMP5 knockout mouse, immunofluorescence, auditory brainstem response (ABR) recording, startle response behavioral assay |
Molecular brain |
High |
30867010
|
| 2022 |
LAMP5 is a direct target of MLL-fusion oncoproteins. In MLL-rearranged leukemia cells, LAMP5 modulates innate immune signaling by transferring signal flux from interferon-signaling endosomes to pro-inflammatory signaling endosomes. LAMP5 depletion inhibits NF-κB signaling, increases type I interferon signaling downstream of TLR/IL-1R activation, and suppresses leukemia cell growth in vitro and in vivo. IRF7 depletion partially rescues growth inhibition caused by LAMP5 knockdown (epistasis). LAMP5 is also detectable on the leukemia cell surface. |
shRNA knockdown, in vitro and in vivo leukemia models, NF-κB and IFN signaling reporter/western blot assays, epistasis experiment (IRF7 depletion rescue), surface protein detection, antibody-drug conjugate treatment |
Haematologica |
High |
33910331
|
| 2023 |
LAMP5 interacts with ANXA7 (an annexin with Ca2+-dependent GTPase activity) in neurons. ANXA7 activation stabilizes LAMP5 protein expression. Asp411 mutation of ANXA7 impairs its interaction with LAMP5. Overexpression of LAMP5 attenuates lysosomal acidification impairment, autophagy inhibition, and apoptosis caused by ANXA7 downregulation after oxygen-glucose deprivation/reperfusion (OGD/R). Together, ANXA7 and LAMP5 regulate autophagy and apoptosis via the mTOR/TFEB pathway. |
Co-immunoprecipitation, site-directed mutagenesis (Asp411), overexpression/knockdown in neuronal cells, autophagy/apoptosis assays, lysosomal acidification assay, mTOR/TFEB pathway western blot |
Cell death discovery |
Medium |
37620352
|
| 2023 |
LAMP5 silencing in multiple myeloma cell lines promotes apoptosis. Mechanistically, LAMP5 may exert pro-tumor effects partly through activation of p38 protein, as assessed by western blotting after LAMP5 knockdown. |
siRNA knockdown, flow cytometry (apoptosis), western blotting (p38 activation) |
Pathology oncology research : POR |
Low |
37033323
|
| 2024 |
LAMP5-AS1 lncRNA recruits DOT1L to the LAMP5 locus to directly activate LAMP5 transcription. Knocking down LAMP5-AS1 enhances autophagic degradation of MLL fusion proteins and inhibits MLL leukemia cell survival in vitro and in vivo. This identifies a lncRNA-DOT1L-LAMP5 regulatory axis. |
ChIRP, RNA pull-down, ChIP, RNA FISH, LC3B puncta/TEM autophagy assays, mRFP-GFP-LC3 autophagic flux, in vivo mouse survival |
Experimental hematology & oncology |
High |
38374003
|
| 2025 |
LAMP5 interacts with IRF4 and prevents its degradation through the autophagy-lysosome pathway in multiple myeloma. LAMP5 also enhances the interaction between IRF4 and the nuclear transport protein KPNA2, facilitating IRF4 nuclear transport and preventing its cytoplasmic retention and subsequent autophagic degradation. Nuclear IRF4 promotes c-MYC transcription, and c-MYC positively feeds back to activate LAMP5 transcription, forming a regulatory loop. High-throughput drug screening identified pyrazofurin as a compound that disrupts the LAMP5-IRF4 interaction, leading to IRF4 degradation. |
Co-immunoprecipitation, autophagy-lysosome pathway inhibition assays, nuclear/cytoplasmic fractionation, western blotting, ChIP, high-throughput drug screening, in vitro and in vivo myeloma models |
Oncogene |
High |
40721659
|
| 2024 |
LAMP5 facilitates bladder cancer cell proliferation via regulation of the FBXW11/p27 axis, as determined by in vitro knockdown experiments. |
siRNA knockdown, proliferation assays, western blotting (FBXW11, p27) |
Apoptosis : an international journal on programmed cell death |
Low |
41663867
|