| 2007 |
MON1A ortholog SAND-1 in C. elegans is essential for RAB-7 function at the transition from early to late endosomes; loss of SAND-1 causes delayed endocytic transport and failure to deliver cargo to lysosomes, while initial RAB-7 recruitment is not affected by SAND-1 loss at lysosomes. |
C. elegans genetics (RNAi, loss-of-function mutants), fluorescence microscopy of endocytic cargo trafficking |
The EMBO journal |
High |
17203072
|
| 2007 |
Mon1a controls vesicular trafficking of ferroportin (the major iron exporter) to the macrophage cell surface; a missense allele of Mon1a (C57BL/10J) reduces surface ferroportin levels, increasing macrophage iron content. Mon1a also affects trafficking of cell-surface and secreted molecules unrelated to iron metabolism, indicating a general role in the mammalian secretory apparatus. |
Quantitative trait locus analysis, congenic mouse lines, cell-based trafficking assays |
Nature genetics |
High |
17632513
|
| 2010 |
MON1A (and its paralog Mon1b) are required for phagosome maturation: phagosomes in Mon1a/b-depleted mammalian cells recruit RAB5 but fail to progress to the RAB7-positive stage. Mon1 interacts with GTP-bound Rab5, identifying Mon1 as a Rab5 effector. A Mon1-Ccz1 complex (but not either protein alone) binds Rab7 and can influence Rab7 activation, linking the Rab5-positive to Rab7-positive stage of phagosome maturation. |
C. elegans genetics, mammalian cell RNAi, Co-immunoprecipitation with GTP/GDP-locked Rab mutants, phagosome maturation assays |
Nature |
High |
20305638
|
| 2012 |
Mon1a functions in anterograde trafficking through the secretory pathway including ER-to-Golgi and Golgi-to-plasma membrane steps. siRNA knockdown delays Golgi reassembly after Brefeldin A treatment and slows ER-to-Golgi transport of ts045VSVG-GFP (confirmed by EndoH sensitivity). Mon1a associates with dynein intermediate chain (by co-immunoprecipitation and mass spectrometry), and reductions in Mon1a or dynein both alter Golgi morphology. |
siRNA knockdown, Brefeldin A reformation assay, ts045VSVG-GFP trafficking assay with EndoH treatment, co-immunoprecipitation, mass spectrometry |
The Journal of biological chemistry |
High |
22665492
|
| 2013 |
Drosophila Mon1 ortholog Dmon1 is required for recruitment of Rab7 to maturing endosomes; loss of Dmon1 causes enlarged maturing endosomes that lose Rab7 association and accumulate transmembrane cargo such as Notch, phenocopying Rab7 loss of function. |
Drosophila genetics (loss-of-function mutants), fluorescence microscopy, electron microscopy of endosomes |
Journal of cell science |
High |
23418349
|
| 2020 |
MON1A is a core component of the trimeric Mon1-Ccz1-C18orf8 (MCC) GEF complex for Rab7. MON1A/B-deficient cells lack Rab7 activation and show severe defects in late endosome morphology and endosomal LDL trafficking. Active Rab7 (dependent on MCC complex) interacts with the NPC1 cholesterol transporter to license lysosomal cholesterol export; this process is abolished in Mon1A/B-deficient cells and restored by constitutively active Rab7. |
Genome-wide CRISPR screen, CRISPR knockout, cholesterol reporter, Rab7 activation assays, co-immunoprecipitation with NPC1, rescue with constitutively active Rab7 |
Nature communications |
High |
33144569
|
| 2020 |
NRBF2 interacts with the CCZ1-MON1A GEF complex and is required for maintaining its GEF activity toward RAB7; NRBF2 regulates CCZ1-MON1A interaction with PI3KC3/VPS34 and CCZ1-associated PI3KC3 kinase activity, which are required for CCZ1-MON1A GEF activity. Loss of NRBF2 impairs autophagosome maturation and APP-CTF degradation via reduced GTP-RAB7 levels on autophagosomes. |
Co-immunoprecipitation, GST-R7BD affinity-isolation (GTP-RAB7 pull-down), NRBF2 knockdown/knockout, autophagosome purification, PI3K activity assay |
Autophagy |
High |
32543313
|
| 2022 |
The lysosomal V-ATPase a3 subunit interacts with the Mon1A-Ccz1 GEF complex; interaction is mediated by the amino-terminal half domain of a3 and the longin motifs of Mon1A and Ccz1. a3 recruits Mon1A-Ccz1 to secretory lysosomes in osteoclasts, which is required for Rab7 activation and subsequent outward trafficking of secretory lysosomes for bone resorption. |
Co-immunoprecipitation in HEK293T cells, Mon1A longin-domain mutants deficient in Rab7 interaction, immunofluorescence of endogenous Ccz1 in a3-deficient osteoclasts |
Scientific reports |
Medium |
35589873
|
| 2022 |
Overexpression of the CCZ1-MON1A GEF complex increases active (GTP-bound) RAB7 in autophagosome fractions, enhances autophagosome maturation, and promotes degradation of APP-CTFs, Aβ, and P-tau in an autophagy-dependent manner in AD cell and mouse models; conversely, knockdown of MON1A impairs autophagosome maturation. |
AAV-mediated stereotaxic brain injection for MON1A/CCZ1 overexpression or knockdown, GST-R7BD affinity-isolation from purified autophagosomes, immunoblotting, 3xTg AD mouse model |
Theranostics |
Medium |
35198070
|
| 2020 |
The GOLD domain of FYCO1 interacts with the CCZ1-MON1A complex; this interaction was identified by AP-MS and validated by co-immunoprecipitation. FYCO1 interaction with CCZ1-MON1A is necessary for RAB7A activation and fusion of autophagosomal/endosomal vesicles with lysosomes. |
Affinity purification-mass spectrometry (spin-tip IMAC columns), co-immunoprecipitation validation, FYCO1 KO/KD functional assays |
Analytical chemistry / Autophagy |
Medium |
31992042 37418591
|
| 2014 |
In C. elegans, the SAND-1/CCZ-1 complex acts as a GEF for RAB-7 to promote HOPS effector activity and late endosome-lysosome fusion. SAND-1 does not participate in gut granule (lysosome-related organelle) formation, indicating that CCZ-1 can partner with a different protein (GLO-3) to activate an alternate Rab (GLO-1) for LRO biogenesis. |
C. elegans genetics (loss-of-function mutants, epistasis), fluorescence microscopy of gut granule protein trafficking |
Molecular biology of the cell |
Medium |
24501423
|
| 2023 |
Mon1a is required for maintenance of Golgi architecture. Mon1a interacts with the F-BAR protein FCHO2 (identified by yeast two-hybrid and co-immunoprecipitation). siRNA-mediated depletion of Mon1a or FCHO2 causes Golgi fragmentation and abolishes exchange of resident membrane proteins between Golgi ministacks (shown by FRAP). Mon1a-silenced Golgi disruption is not cell cycle-dependent, unlike FCHO2-silenced disruption. Mon1a thus generates lateral links between Golgi ministacks to create Golgi ribbons. |
Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, fluorescence microscopy, FRAP analysis |
bioRxivpreprint |
Medium |
37461455
|
| 2025 |
MON1A variants were identified as causal for congenital diarrhea and enteropathy (CODEs) in human infants; functional characterization in cell and zebrafish models confirmed a role for MON1A in intestinal epithelial function. |
Exome/genome sequencing, cell models, zebrafish models with variant functional testing |
The New England journal of medicine |
Medium |
40174224
|
| 2024 |
GORASP2 controls RAB7A activity by modulating its GEF complex MON1A-CCZ1, thereby impacting RAB7A's interaction with the HOPS complex and autophagosome maturation. |
siRNA depletion of GORASP2, RAB7A activity assays, Co-IP, super-resolution microscopy |
Autophagy |
Medium |
39056394
|
| 2025 |
In C. elegans, ubiquitinated proteins on the endosomal limiting membrane prevent displacement of the Rab5 GEF RABX-5 by the Rab7 GEF SAND-1/CCZ-1, thus upstream ESCRT-0 activity and ubiquitinated cargo act as timers for the onset of Rab conversion mediated by SAND-1/CCZ-1. |
C. elegans genetics (loss-of-function, epistasis), fluorescence microscopy, Rab7 overexpression rescue |
The EMBO journal |
Medium |
39910226
|