| 2001 |
RILP (Rab7-interacting lysosomal protein) specifically binds GTP-bound Rab7 and recruits functional dynein-dynactin motor complexes to late endosomes and lysosomes, causing their transport toward microtubule minus ends and inhibiting peripheral trafficking. |
Co-immunoprecipitation, overexpression in mammalian cells, fluorescence microscopy, dominant-negative constructs |
Current Biology |
High |
11696325
|
| 2001 |
RILP is a 45 kDa protein containing two coiled-coil regions, found mainly in cytosol, that is recruited to late endosomal/lysosomal membranes by Rab7-GTP via its C-terminus; RILP-C33 (truncated C-terminal form lacking N-terminal half) acts as dominant negative, inhibiting EGF and LDL degradation and dispersing lysosomes similarly to dominant-negative Rab7. |
Yeast two-hybrid, GST pulldown, overexpression of truncation mutants, degradation assays |
The EMBO Journal |
High |
11179213
|
| 2003 |
RILP promotes extension of phagosomal tubules toward late endocytic compartments by recruiting dynein-dynactin; a truncated RILP lacking the dynein-dynactin-recruiting domain prevents tubule extension and phagosome-lysosome fusion, establishing RILP as essential for phagosome maturation. |
Fluorescence microscopy, electron microscopy, overexpression of RILP truncation mutants, functional phagosome maturation assays |
Molecular and Cellular Biology |
High |
12944476
|
| 2003 |
A unique 62-residue region (amino acids 272–333) in RILP is necessary and sufficient for regulating lysosomal morphology and for interaction with GTP-bound Rab7 and Rab34; transferring this region into the related protein RLP1 confers lysosome-regulatory activity. |
Domain swapping/chimeric protein expression, GTPase interaction assays, lysosome morphology readout in mammalian cells |
Molecular Biology of the Cell |
High |
14668488
|
| 2004 |
Salmonella effector SifA disrupts the Rab7–RILP interaction on Salmonella-containing vacuoles, preventing dynein recruitment; this uncoupling allows kinesin-dependent centrifugal extension of Salmonella-induced filaments, promoting bacterial replication in a protected compartment. |
Co-transfection, immunofluorescence, immobilized RILP pulldown of active Rab7, cell-free system with BCG supernatant |
Molecular Biology of the Cell |
High |
15121880
|
| 2007 |
GTP-bound Rab7 simultaneously binds RILP and ORP1L to form a tripartite RILP-Rab7-ORP1L complex; RILP directly contacts the C-terminal 25-kDa region of dynactin p150Glued; ORP1L and betaIII spectrin are additionally required for dynein motor activity, establishing a stepwise assembly cascade for minus-end endosomal transport. |
Co-immunoprecipitation, GST pulldown, siRNA knockdown, live-cell imaging, dominant-negative constructs |
The Journal of Cell Biology |
High |
17283181
|
| 2007 |
RILP is required for biogenesis of multivesicular endosomes (MVEs): RILP depletion by siRNA reduces intralumenal vesicle content, impairs EGFR degradation (but not transferrin recycling), and causes elevated levels of late-endosomal markers. RILP interacts with ESCRT-II subunits Vps22 and Vps36. |
siRNA knockdown, electron microscopy, degradation assays for EGFR vs. transferrin, co-immunoprecipitation with ESCRT-II subunits |
Journal of Cell Science |
High |
17959629
|
| 2006 |
RILP interacts with VPS22 (EAP30/SNF8) of ESCRT-II via its N-terminal half, and with VPS36 (EAP45) via its C-terminal half; RILP overexpression causes enlarged, clustered MVBs and retards EGF sorting at sorting endosomes, suggesting a regulatory loop between early and late endocytic machinery. |
Yeast two-hybrid, co-immunoprecipitation, confocal immunofluorescence, RILP domain truncation analysis |
Biochemical and Biophysical Research Communications |
Medium |
16857164 17010938
|
| 2007 |
Mycobacterium bovis BCG inhibits phagosome maturation by preventing RILP recruitment to Rab7 on phagosomal membranes; BCG culture supernatant contains a factor that catalyzes GTP→GDP conversion on Rab7, maintaining Rab7 in inactive GDP-bound form and blocking RILP-mediated lysosomal fusion. |
Co-transfection, immobilized RILP pulldown of GTP-bound Rab7, cell-free GTPase activity assay |
Journal of Leukocyte Biology |
Medium |
18040083
|
| 2008 |
Huntingtin regulates REST/NRSF nuclear trafficking indirectly through a complex containing REST/NRSF, RILP, dynactin p150Glued, huntingtin, and HAP1; RILP directly binds p150Glued and REST/NRSF; mutant huntingtin weakens the dynactin p150Glued–RILP interaction; HAP1 prevents the complex from translocating REST/NRSF to the nucleus. |
Yeast two-hybrid, co-immunoprecipitation of in vitro translated proteins, complex characterization |
The Journal of Biological Chemistry |
Medium |
18922795
|
| 2009 |
Cholesterol levels in late endosomes are sensed by ORP1L; under low cholesterol, ORP1L conformation induces formation of ER-late endosome membrane contact sites where VAP (ER protein) interacts in trans with the Rab7-RILP complex to remove p150Glued and associated motors, causing plus-end directed movement. High cholesterol (as in Niemann-Pick C) prevents this, locking LEs at minus-end via dynein-RILP. |
Co-immunoprecipitation, dominant-negative constructs, fluorescence microscopy, fractionation, cholesterol manipulation |
The Journal of Cell Biology |
High |
19564404
|
| 2012 |
RILP functions as an effector of Rab36 (in addition to Rab7) via its RILP homology domain (RHD, a coiled-coil domain); site-directed mutagenesis of RHD revealed differential amino acid contributions to Rab7 vs. Rab36 binding; Rab36-RILP interaction mediates retrograde melanosome transport in melanocytes, independent of Rab7. |
Yeast two-hybrid screen, GST pulldown, site-directed mutagenesis, knockdown in melanocytes, melanosome distribution assays |
The Journal of Biological Chemistry |
High |
22740695
|
| 2012 |
Melanoregulin (Mreg) interacts with the C-terminal domain of RILP and forms a trimeric complex with RILP and p150Glued, mediating dynein-dynactin-dependent retrograde melanosome transport; Mreg knockdown or dynein-dynactin disruption restores peripheral melanosome distribution in Rab27A-deficient melanocytes. |
Co-immunoprecipitation, siRNA knockdown, overexpression, melanosome distribution assays |
Journal of Cell Science |
Medium |
22275436
|
| 2013 |
RILP simultaneously and directly binds both the HOPS tethering complex and p150Glued subunit of dynein-dynactin, coupling late endosomal transport and tethering into a single RAB7-RILP-ORP1L multiprotein complex; ORP1L acts as a cholesterol-sensing switch controlling RILP-HOPS-p150Glued interactions. |
Co-immunoprecipitation, siRNA knockdown, genetic epistasis (haploid cell screen), Ebola infection assay, in vitro binding |
Journal of Cell Science |
High |
23729732
|
| 2014 |
RILP interacts with the V1G1 subunit (ATP6V1G1) of vacuolar ATPase, controls V1G1 recruitment to late endosomal/lysosomal membranes, promotes proteasomal degradation of V1G1 (via ubiquitylation), and thereby regulates V-ATPase assembly and activity. |
Co-immunoprecipitation, siRNA knockdown, V-ATPase activity assay, ubiquitylation assay, fluorescence microscopy |
Journal of Cell Science |
High |
24762812
|
| 2015 |
RILP suppresses breast cancer cell invasion by interacting with RalGDS (Ral guanine nucleotide dissociation stimulator) via its N-terminal region; this interaction recruits RalGDS to late endosomes, inhibiting its GEF activity toward RalA and thereby suppressing invasion. |
Co-immunoprecipitation, truncation analysis, immunofluorescence, RalA activity assay, siRNA knockdown, migration/invasion assays |
Cell Death & Disease |
Medium |
26469971
|
| 2016 |
Folliculin (FLCN) promotes perinuclear lysosome clustering by interacting directly via its C-terminal DENN domain with RILP; purified FLCN-DENN domain loads active Rab34 onto RILP (but does not act as a GEF for Rab34); this drives formation of Rab34-positive membrane contacts with lysosomes reducing their motility. |
Purified recombinant protein in vitro binding assay, siRNA knockdown, live-cell imaging, co-immunoprecipitation |
EMBO Reports |
High |
27113757
|
| 2016 |
HCV (and Sendai virus) infection causes NS3/4A protease-dependent cleavage of RILP, generating a C-terminal fragment (cRILP) that lacks the N-terminus; cRILP redistributes to the cell periphery, releases from dynein p150Glued, and redirects Rab7 vesicles to kinesin-dependent trafficking, promoting virion secretion. |
Viral infection, western blot for RILP cleavage, siRNA knockdown, cRILP expression, kinesin inhibitor, trafficking assays |
Proceedings of the National Academy of Sciences |
High |
27791088
|
| 2016 |
Rab12 is a novel binding partner and cargo of RILP; activated Rab12 interacts with RILP to mediate microtubule-dependent retrograde transport of mast cell secretory granules via the RILP-dynein complex; Rab12 negatively regulates mast cell degranulation through this mechanism. |
Co-immunoprecipitation, siRNA knockdown, live-cell imaging, dominant-negative constructs, degranulation assays |
Journal of Immunology |
Medium |
26740112
|
| 2018 |
Caspase-1 directly cleaves RILP at aspartic acid 75; alanine substitution at D75 blocks caspase-1-mediated cleavage; redistribution of cleaved RILP to the cytoplasm requires both cleavage and specific phosphorylation events near the caspase-1 site; combined cleavage + phosphorylation are required for release from dynein p150Glued and redistribution of CD63-positive vesicles. |
In vitro caspase-1 cleavage assay, site-directed mutagenesis (D75A), phosphorylation analysis, localization by fluorescence microscopy |
Biochemical and Biophysical Research Communications |
Medium |
30100068
|
| 2018 |
Rab7 interacts with ORP1L via a non-canonical site (helix3 and 310-helix2 of Rab7), independently of GTP/GDP state; this leaves the canonical effector-interacting switch regions free for RILP binding, enabling simultaneous ORP1L-Rab7-RILP tripartite complex formation; mutational disruption of the ORP1L-Rab7 interface impairs late endosome positioning. |
Crystal structure of Rab7-ORP1L ARDN, biochemical binding assays, mutagenesis, late endosome positioning assay |
The Journal of Biological Chemistry |
High |
30012887
|
| 2019 |
LRRK1 phosphorylates GTP-bound Rab7 at serine 72 at endosomal membranes; this phosphorylation promotes RILP interaction with Rab7, leading to dynein-dynactin recruitment and dynein-driven transport of EGFR-containing endosomes to the perinuclear region. |
In vitro kinase assay, phospho-specific antibody, co-immunoprecipitation, LRRK1 knockdown/overexpression, endosome transport assay |
Journal of Cell Science |
High |
31085713
|
| 2019 |
RILP interacts with insulin granule-associated Rab26 and mediates lysosomal degradation of proinsulin; RILP overexpression induces insulin granule clustering and promotes Rab7-dependent, lysosomal inhibitor-sensitive proinsulin degradation, thereby restricting insulin secretion. |
Co-immunoprecipitation, overexpression, siRNA knockdown, lysosomal inhibitor treatment, insulin secretion assays in beta-cell lines and islets |
Diabetes |
Medium |
31624142
|
| 2020 |
RILP functions as a dynein adaptor for neuronal autophagosomes and controls autophagosome biogenesis: mTOR inhibition upregulates RILP expression and its localization to autophagosomes; RILP interacts with ATG5 on isolation membranes (preventing premature dynein recruitment) and with LC3 via LIR motifs; RILP depletion or LIR motif mutation strongly reduces autophagosome numbers and impairs autophagic turnover. |
siRNA knockdown, LIR motif mutagenesis, co-immunoprecipitation with ATG5 and LC3, live-cell imaging, autophagy flux assays |
Developmental Cell |
High |
32275887
|
| 2021 |
Biochemical and in silico analysis reveals that Rab12 interacts with the RILP homology domain (RHD) of one RILP monomer and a C-terminal threonine of the other RILP monomer in a homodimeric RILP complex; lysine-71 of Rab12 is critical for binding RILP-L1 and RILP-L2 but dispensable for RILP binding; mutational analyses of RILP RHD demonstrate its involvement in mast cell secretory granule transport regulation. |
Molecular dynamics simulations, functional mutagenesis, peptide inhibition assays, biochemical binding assays |
Scientific Reports |
Medium |
33986343
|
| 2024 |
DENND6A acts as a GEF for Rab34 and as an effector of Arl8b; Arl8b recruits DENND6A to peripheral lysosomes, where it activates Rab34, which in turn recruits a RILP/dynein complex to drive lysosome retrograde transport and juxtanuclear repositioning; loss of DENND6A impairs autophagic flux. |
Cell-based GEF screen, co-immunoprecipitation, siRNA knockdown, lysosome positioning assay, autophagic flux assay |
Nature Communications |
High |
38296963
|
| 2024 |
Rab7 phosphorylation at tyrosine 183 in diabetic cardiomyopathy promotes RILP recruitment to lipid droplets, enabling lysosomal degradation of lipid droplets via microlipophagy; Rab7 activator ML-098 enhances RILP levels and rescues cardiac dysfunction. |
RNA-seq, conditional knockout mice, phospho-specific analysis, in vivo pharmacological intervention, cardiac functional assays |
Advanced Science |
Medium |
38837607
|
| 2024 |
RILP induces late endosome/lysosome clustering that reduces ER-endolysosome contact sites; RILP interacts with ORP1L to competitively inhibit VAP-ORP1L contact site formation, blocking cholesterol flow from endolysosomes to ER and triggering RILP-dependent autophagy. |
Co-immunoprecipitation, immunofluorescence microscopy, cholesterol assays, autophagy assays, overexpression |
Cells |
Medium |
39195203
|
| 2024 |
pH neutralization of late endosomes increases V1G1 (ATP6V1G1) subunit assembly on endosomal membranes; V1G1 stabilizes GTP-bound Rab7 via RILP interaction, leading to Rab7 hyperactivation, disrupted tubulation, and impaired CI-M6PR recycling, defining a V-ATPase–RILP–Rab7 feedback axis for endosomal pH control. |
LLOMe and NH4Cl treatments, dominant-active Rab7 mutants, co-immunoprecipitation, live-cell imaging, mannose-6-phosphate receptor trafficking assay |
Journal of Cell Science |
Medium |
38578235
|
| 2025 |
RILP functions as a RAB7A-dependent dynein adaptor for late endosome motility in neuronal dendrites, promotes endosome carrier formation, and is required for retrograde transport and clearance of degradative cargos from dendrites; importantly, RAB7A-RILP interaction is not required for lysosomal fusion or somatic degradation, but RAB7A/RILP-dependent late endosome transport is required for dendrite arborization. |
Separation-of-function RAB7A-L8A mutant (RILP-binding deficient) expressed in hippocampal neurons, live-cell imaging, cargo degradation assays, dendrite morphology analysis |
bioRxivpreprint |
Medium |
bio_10.1101_2025.09.03.673267
|