Affinage

RILP

Prickle-like protein 1 · UniProt Q96MT3

Audit flag: ungrounded claim
Length
831 aa
Mass
94.3 kDa
Annotated
2026-06-10
62 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RILP is a Rab effector that converts the GTP-loaded state of late endosomal/lysosomal small GTPases into directed minus-end microtubule transport, coupling organelle motility with tethering, fusion, and maturation (PMID:11179213, PMID:11696325, PMID:17283181). It is recruited to late endosomal and lysosomal membranes by GTP-bound Rab7 through a defined Rab-homology region (residues ~272–333) and acts as a dynein adaptor by directly binding the C-terminal 25-kDa region of the dynactin subunit p150Glued, thereby recruiting the dynein-dynactin motor to drive centripetal transport of late endosomes, lysosomes, and phagosomes (PMID:11179213, PMID:14668488, PMID:12944476, PMID:17283181). Productive dynein activation requires assembly of a tripartite Rab7-RILP-ORP1L complex, with ORP1L acting as a cholesterol-sensing switch: under low cholesterol ORP1L promotes ER-endosome VAP contacts that strip p150Glued from the Rab7-RILP complex, while RILP can competitively inhibit VAP-ORP1L contact formation, integrating organelle positioning with sterol status (PMID:17283181, PMID:19564404, PMID:23729732, PMID:30012887, PMID:39195203). RILP simultaneously engages the HOPS tethering complex to couple transport with endolysosomal fusion, interacts with ESCRT-II subunits VPS22 and VPS36 to support multivesicular body biogenesis and EGFR degradation, and binds the V-ATPase peripheral-stalk subunit V1G1 (ATP6V1G1) to control its membrane recruitment, ubiquitylation-dependent turnover, and V-ATPase activity (PMID:16857164, PMID:17010938, PMID:17959629, PMID:23729732, PMID:24762812). The same adaptor module is used by additional Rab GTPases — Rab34, Rab36, Rab12, and Rab26 — to position lysosomes, melanosomes, secretory granules, and insulin granules, and RILP is required for retrograde transport and biogenesis of autophagosomes via LIR-dependent LC3 binding and ATG5 interaction (PMID:22740695, PMID:27113757, PMID:26740112, PMID:31624142, PMID:32275887). RILP activity is controlled post-translationally: LRRK1 phosphorylation of Rab7 on Ser72 enhances Rab7-RILP binding, while caspase-1 cleavage at Asp75, together with nearby phosphorylation, releases RILP from p150Glued and redistributes vesicles to the cell periphery, a mechanism exploited by HCV and inflammatory states to redirect trafficking (PMID:27091088, PMID:30100068, PMID:31085713, PMID:40137558).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    Established that RILP is the downstream effector translating Rab7 activation into lysosomal transport, answering how the Rab7 GTPase switch is read out functionally.

    Evidence Yeast two-hybrid, GST pulldown, co-IP, and dominant-negative epistasis with degradation assays in mammalian cells

    PMID:11179213 PMID:11696325

    Open questions at the time
    • Did not identify the motor-recruiting partner directly
    • Structural basis of Rab7-GTP recognition not resolved
  2. 2003 High

    Mapped a unique ~62-residue region sufficient for Rab7/Rab34 binding and lysosomal morphology control, defining the modular Rab-homology element that confers effector activity.

    Evidence Truncation/chimeric mutants transferred into RLP1 with lysosomal morphology and GTPase-binding assays; phagosome maturation imaging

    PMID:12944476 PMID:14668488

    Open questions at the time
    • Did not define the dynein-recruiting interface at residue level
    • Mechanism of tubule extension during phagosome maturation incomplete
  3. 2007 High

    Identified p150Glued as the direct RILP partner and showed dynein activation needs additional ORP1L/betaIII-spectrin factors, refining RILP from a simple motor bridge to part of a multi-component activation module.

    Evidence Reciprocal co-IP, GST pulldown, deletion mutants, and organelle motility assays; RNAi loss-of-function with EM and cargo trafficking

    PMID:17283181 PMID:17959629

    Open questions at the time
    • How betaIII-spectrin triggers dynein activation mechanistically unresolved
    • Stoichiometry of the Rab7-RILP-p150Glued-ORP1L complex unknown
  4. 2006 Medium

    Connected RILP to ESCRT-II via VPS22 and VPS36 binding, linking late endosomal transport to MVB sorting machinery.

    Evidence Yeast two-hybrid, co-IP, colocalization, and EGF sorting assays across two concurrent papers

    PMID:16857164 PMID:17010938

    Open questions at the time
    • Functional consequence of ESCRT-II binding for ILV formation not mechanistically dissected
    • Single-lab observations without structural validation
  5. 2009 High

    Revealed cholesterol sensing through ORP1L as the switch governing RILP-dependent endosome positioning, explaining how lipid status controls motor recruitment.

    Evidence Co-IP, organelle motility assays, and NPC disease cell model with cholesterol manipulation

    PMID:19564404

    Open questions at the time
    • How VAP trans-interaction physically removes p150Glued not resolved at structural level
  6. 2013 High

    Showed RILP concomitantly binds HOPS and p150Glued, coupling transport and fusion into one complex and explaining its role in viral entry requiring endolysosomal fusion.

    Evidence Co-IP, direct binding assays, knockdown, and Ebola virus infection assay

    PMID:23729732

    Open questions at the time
    • Temporal ordering of HOPS vs dynein engagement on a single organelle unknown
  7. 2012 High

    Demonstrated that the RILP Rab-homology domain reads multiple Rab GTPases (Rab36 for melanosomes), generalizing RILP as a shared adaptor for different organelle transport systems.

    Evidence Yeast two-hybrid, GST pulldown, site-directed mutagenesis, and melanosome distribution assays; Mreg interaction with melanosome readout

    PMID:22275436 PMID:22740695

    Open questions at the time
    • Determinants of Rab selectivity in vivo incompletely defined
    • Mreg's regulatory mechanism on dynein not resolved
  8. 2014 High

    Identified V1G1 as a RILP target whose stability and membrane recruitment RILP controls, extending RILP function to regulation of V-ATPase-dependent acidification.

    Evidence Yeast two-hybrid, co-IP, ubiquitylation assays, and V-ATPase activity measurements

    PMID:24762812

    Open questions at the time
    • Identity of the ubiquitin ligase acting on V1G1 not established
    • Link between acidification control and transport not integrated
  9. 2016 High

    Expanded the RILP Rab repertoire to Rab34 (via FLCN), Rab12, and other GTPases and connected RILP-loss to viral exploitation through HCV-induced cleavage redirecting trafficking peripherally.

    Evidence Purified recombinant binding assays, co-IP, knockdown, live imaging; viral infection with cRILP overexpression and kinesin inhibition

    PMID:26740112 PMID:27091088 PMID:27113757

    Open questions at the time
    • Identity of the protease producing cRILP in HCV infection not defined here
    • How FLCN-DENN promotes complex formation without GEF activity unclear
  10. 2018 High

    Defined caspase-1 cleavage at Asp75 plus adjacent phosphorylation as the inactivating switch that releases RILP from p150Glued, providing a regulated mechanism to redistribute vesicles to the periphery.

    Evidence In vitro caspase-1 cleavage with D75A mutagenesis, phosphorylation analysis, and CD63 vesicle imaging; crystal structure of ORP1L-Rab7 interface with positioning assays

    PMID:30012887 PMID:30100068

    Open questions at the time
    • Kinase responsible for the priming phosphorylation not identified
    • Physiological triggers of caspase-1-mediated RILP cleavage beyond viral context unclear
  11. 2019 High

    Showed Rab7 phosphorylation (LRRK1 on Ser72) enhances Rab7-RILP binding, establishing kinase-regulated control of motor recruitment.

    Evidence In vitro kinase assay, phospho-specific antibodies, co-IP, and endosomal transport assays with LRRK1 knockdown

    PMID:31085713

    Open questions at the time
    • Whether other Rab kinases similarly tune RILP affinity not addressed
  12. 2020 High

    Established RILP as essential not only for autophagosome retrograde transport but unexpectedly for their biogenesis, via LIR-dependent LC3 binding and ATG5 interaction that delays premature dynein recruitment.

    Evidence RNAi knockdown, LIR motif mutagenesis, co-IP with ATG5/LC3, autophagosome counting, and p62 flux assays in neurons

    PMID:32275887

    Open questions at the time
    • How RILP contributes mechanistically to isolation membrane formation unresolved
    • Relationship between biogenesis and transport roles not separated
  13. 2024 Medium

    Integrated RILP into broader physiology — insulin granule degradation via Rab26, lysosome positioning via the Arl8b-DENND6A-Rab34 axis, V-ATPase/pH-coupled Rab7 hyperactivation, ER-contact competition with ORP1L, and inflammation/tau and cancer roles.

    Evidence Co-IP, knockdown/overexpression, GEF screens, cholesterol/autophagy assays, and disease models (diabetes, osteosarcoma, NSCLC, AD-related tau)

    PMID:31624142 PMID:37789274 PMID:38296963 PMID:38578235 PMID:39195203

    Open questions at the time
    • Many disease links rely on single-lab overexpression/knockdown
    • Direct biochemical role of RILP in several inferred axes not always assayed
  14. 2025 Medium

    Separated RILP transport from degradation functions using a RILP-binding-deficient Rab7 mutant, showing dendritic late endosome motility and arborization require RILP but somatic degradation does not.

    Evidence Separation-of-function RAB7A-L8A mutant in hippocampal neurons with live imaging and dendrite/cargo assays (preprint); caspase-1-cleaved RILP impairs microglial tau degradation and propagation

    PMID:40137558 PMID:bio_10.1101_2025.09.03.673267

    Open questions at the time
    • Preprint not yet peer-reviewed
    • How transport and degradation roles diverge mechanistically remains open

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple RILP partner interactions (Rab GTPases, p150Glued, HOPS, ORP1L, ESCRT-II, V1G1) are spatially and temporally ordered on a single maturing organelle, and the structure of the assembled motor-tethering supercomplex, remain unresolved.
  • No high-resolution structure of the full RILP-containing transport/fusion supercomplex
  • Quantitative interplay among competing RILP interactions during organelle maturation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005764 lysosome 3 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 3 R-HSA-9612973 Autophagy 3
Partners
ATP6V1G1DCTN1/P150GLUEDORP1LRAB34RAB36RAB7AVPS22VPS36
Complex memberships
ESCRT-II (VPS22/VPS36)HOPS tethering complexRab7-RILP-ORP1L tripartite complexdynein-dynactin (p150Glued) motor complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 RILP (Rab7-interacting lysosomal protein) specifically binds the GTP-bound (active) form of Rab7 at its C-terminus, is recruited to late endosomal/lysosomal membranes by Rab7-GTP, and functions as a downstream effector of Rab7 required for transport to lysosomes. Expression of a truncated form (RILP-C33) lacking the N-terminal half inhibits EGF and LDL degradation and disperses lysosomes, similar to Rab7 dominant-negative mutants; full-length RILP rescues Rab7 dominant-negative effects. Yeast two-hybrid screen, GST pulldown, co-immunoprecipitation, mammalian cell overexpression/dominant-negative epistasis, degradation assays The EMBO journal High 11179213
2001 RILP expression induces the recruitment of functional dynein-dynactin motor complexes to Rab7-containing late endosomes and lysosomes, driving minus-end microtubule transport and inhibiting transport toward the cell periphery. RILP also prevents further cycling of Rab7. Overexpression of RILP in cells, immunofluorescence, live imaging of organelle transport, functional dynein-dynactin recruitment assays Current biology : CB High 11696325
2003 A unique 62-residue region (amino acids 272–333) within RILP is necessary and sufficient for regulating lysosomal morphology and for interaction with GTP-bound Rab7 and Rab34. Transfer of this region into the related protein RLP1 confers lysosome-regulating activity on RLP1. Truncation/chimeric mutant overexpression, lysosomal morphology assays, GTPase binding assays Molecular biology of the cell High 14668488
2003 RILP bridges phagosomes with dynein-dynactin via active Rab7, promoting centripetal phagosome movement and extension of phagosomal tubules toward late endocytic compartments. A truncated RILP lacking the dynein-dynactin-recruiting domain prevents tubule extension and fusion with late endosomes/lysosomes. Fluorescence microscopy, electron microscopy, dominant-negative RILP expression, phagosome maturation assays Molecular and cellular biology High 12944476
2004 Salmonella effector SifA uncouples RILP from active Rab7 on Salmonella-induced filaments (Sifs), preventing dynein recruitment and allowing kinesin-driven centrifugal tubule extension. In vitro experiments indicated SifA may interact with Rab7 to catalyze GDP loading, inactivating it and preventing RILP recruitment. Co-transfection, fluorescence microscopy, in vitro pull-down of active Rab7 with immobilized RILP, cell-free system with BCG/SifA supernatant Molecular biology of the cell Medium 15121880
2006 RILP interacts with VPS22 (EAP30/SNF8) of the ESCRT-II complex; the N-terminal half of RILP mediates this interaction. RILP overexpression leads to enlarged, clustered multivesicular bodies and retards EGF sorting to degradation at EEA1-positive sorting endosomes. Yeast two-hybrid, co-immunoprecipitation, confocal immunofluorescence, EGF trafficking assays Biochemical and biophysical research communications Medium 16857164 17010938
2006 RILP interacts with both VPS22 and VPS36 of ESCRT-II (N-terminal half binds VPS22; C-terminal half binds VPS36), integrating late endocytic machinery with early MVB sorting machinery. Co-immunoprecipitation, overexpression studies, EGF sorting assays Biochemical and biophysical research communications Medium 17010938
2007 RILP directly interacts with the C-terminal 25-kDa region of the dynactin subunit p150Glued, recruiting dynein motor to late endocytic compartments. GTP-bound Rab7 simultaneously binds RILP and ORP1L to form a tripartite RILP-Rab7-ORP1L complex. p150Glued recruitment by Rab7-RILP alone is insufficient for dynein-driven minus-end transport; ORP1L and betaIII spectrin are additionally required — RILP transfers the Rab7-RILP-p150Glued complex to betaIII spectrin to activate dynein. Co-immunoprecipitation, GST pulldown, deletion mutants, organelle motility assays, dominant-negative expression The Journal of cell biology High 17283181
2007 RILP depletion impairs biogenesis of multivesicular endosomes (reduces intraluminal vesicle content), inhibits ligand-mediated EGFR degradation, and causes accumulation of late-endosomal markers (LBPA, Lamp1, CD63, CI-M6PR). Transferrin receptor recycling is not affected by RILP depletion. RNAi knockdown, electron microscopy, immunofluorescence, EGF/transferrin receptor trafficking assays Journal of cell science High 17959629
2007 Mycobacterium bovis BCG inhibits RILP recruitment to phagosomes despite Rab7 acquisition, by promoting GDP-bound (inactive) Rab7. A factor in BCG culture supernatant catalyzes GTP/GDP exchange on Rab7, preventing RILP-mediated lysosomal fusion. This was demonstrated using immobilized RILP to pull down active (GTP-bound) Rab7 from macrophage lysates. Co-transfection, RILP pulldown assay for active Rab7, cell-free system with BCG supernatant, fluorescence microscopy Journal of leukocyte biology Medium 18040083
2008 RILP forms a complex with dynactin p150Glued and REST/NRSF (via its LIM domain), facilitating nuclear translocation of REST/NRSF. Mutant huntingtin weakens the RILP-p150Glued interaction, impairing the complex. HAP1 prevents the complex from translocating REST/NRSF to the nucleus. Huntingtin interacts with p150Glued but not directly with RILP. Yeast two-hybrid, co-immunoprecipitation of in vitro translated proteins, cell-based co-IP The Journal of biological chemistry Medium 18922795
2009 ORP1L senses cholesterol levels in late endosomes (LEs): under low cholesterol conditions, ORP1L conformation induces ER-LE membrane contact sites where the ER protein VAP interacts in trans with the Rab7-RILP complex to remove p150Glued and associated dynein motors, causing LEs to move to microtubule plus ends. Under high cholesterol (e.g., Niemann-Pick type C), this contact is prevented and dynein activity clusters LEs at the minus end. Co-immunoprecipitation, fluorescence microscopy, organelle motility assays, NPC disease cell model, cholesterol manipulation The Journal of cell biology High 19564404
2012 RILP interacts with the Rab7-binding RILP homology domain (RHD), and this domain also mediates interaction with Rab36. RILP expression in melanocytes induces perinuclear melanosome aggregation dependent on Rab36 (not Rab7); Rab36 knockdown disperses melanosomes in Rab27A-deficient melanocytes. Site-directed mutagenesis of the RHD identified distinct amino acid contributions to Rab7 vs. Rab36 binding. Yeast two-hybrid screen, GST pulldown, site-directed mutagenesis, RNAi knockdown, melanosome distribution assays The Journal of biological chemistry High 22740695
2012 Melanoregulin (Mreg) interacts with the C-terminal domain of RILP and forms a complex with RILP and p150Glued in cells. Mreg overexpression or RILP overexpression induces perinuclear melanosome aggregation; Mreg knockdown or functional disruption of dynein-dynactin restores peripheral distribution in Rab27A-deficient melanocytes, identifying Mreg as a regulator of RILP-p150Glued-dynein-dependent retrograde melanosome transport. Co-immunoprecipitation, overexpression, RNAi knockdown, melanosome distribution assays Journal of cell science Medium 22275436
2013 RILP directly and concomitantly binds the tethering HOPS complex and the p150Glued dynactin subunit, linking late endosomal transport and fusion into a single multiprotein complex (RAB7-RILP-ORP1L). ORP1L acts as a cholesterol-sensing switch controlling RILP-HOPS-p150Glued interactions. RILP and ORP1L also control Ebola virus infection, which depends on late endosomal fusion. Co-immunoprecipitation, direct binding assays, overexpression/knockdown, viral infection assay Journal of cell science High 23729732
2014 RILP interacts with V1G1 (ATP6V1G1), a subunit of the peripheral stalk of vacuolar ATPase (V-ATPase). RILP regulates V1G1 recruitment to late endosomal/lysosomal membranes and controls V1G1 stability by promoting its ubiquitylation and proteasomal degradation. Alterations in V1G1 expression impair V-ATPase activity. Yeast two-hybrid, co-immunoprecipitation, overexpression/knockdown, ubiquitylation assays, V-ATPase activity assays Journal of cell science High 24762812
2015 RILP interacts with RalGDS (Ral guanine nucleotide dissociation stimulator) via its N-terminal region binding the GEF domain of RalGDS, recruiting RalGDS to late endosomal compartments. RILP overexpression inhibits RalA activity (a downstream target of RalGDS), suppressing breast cancer cell migration and invasion. Co-immunoprecipitation, truncation mapping, immunofluorescence microscopy, RalA activity assay, migration/invasion assays, RNAi knockdown Cell death & disease Medium 26469971
2016 RILP is a direct effector of Rab34: FLCN (folliculin) interacts with RILP via its C-terminal DENN domain and loads active Rab34 onto RILP using purified recombinant proteins. This Rab34-RILP complex mediates starvation-induced peri-nuclear lysosome clustering. FLCN-DENN does not act as a GEF for Rab34 but rather promotes Rab34-RILP complex formation. Purified recombinant protein binding assays, co-immunoprecipitation, knockdown, live-cell imaging of lysosome distribution EMBO reports High 27113757
2016 HCV (and Sendai virus) infection causes cleavage of RILP, generating a cleaved fragment (cRILP) missing the N-terminus that re-localizes to the cell periphery. Both RILP knockdown and cRILP expression reproduce HCV-induced inhibition of Rab7-dependent endosome-lysosome fusion. cRILP promotes virion secretion via kinesin-dependent trafficking; restoring full-length RILP reverses the trafficking defect. Viral infection, RILP knockdown, cRILP overexpression, kinesin inhibitor treatment, vesicular trafficking assays, fluorescence microscopy Proceedings of the National Academy of Sciences of the United States of America High 27091088
2016 Rab12 is a novel effector of RILP: GTP-bound Rab12 interacts with RILP and mediates minus-end retrograde transport of mast cell secretory granules via the RILP-dynein complex in a stimulus-dependent manner. Co-immunoprecipitation, GTPase pulldown, RNAi knockdown, overexpression, granule transport assays Journal of immunology Medium 26740112
2017 RILP (and Rab7, Rab11) regulates intracellular trafficking of the CMA receptor LAMP2A. The truncated RILP-C33 form cannot rescue defective LAMP2A trafficking in cystinosis, while full-length RILP restores LAMP2A localization at lysosomes. Dominant-negative Rab7 or Rab11 impairs LAMP2A trafficking. Overexpression of wild-type and mutant RILP, dominant-negative constructs, immunofluorescence, knockdown studies in cystinotic cells The Journal of biological chemistry Medium 28465352
2018 Caspase-1 directly cleaves RILP at aspartic acid 75; alanine substitution at D75 blocks caspase-1-mediated cleavage. Cleavage alone is insufficient to re-localize RILP; combined cleavage and phosphorylation near the recognition site are required for redistribution of RILP from perinuclear vesicles throughout the cytoplasm and release from dynactin p150Glued, leading to redistribution of CD63+ intracellular vesicles. Caspase-1 cleavage assay, site-directed mutagenesis (D75A), phosphorylation analysis, immunofluorescence of RILP and CD63 vesicles Biochemical and biophysical research communications High 30100068
2018 Structural and biochemical analysis revealed that Rab7 interacts with ORP1L's N-terminal ankyrin repeat domain (ARDN) independently of Rab7's GTP/GDP binding state, via a unique helix3/310-helix2 region. This leaves Rab7's canonical effector-binding switch regions free to bind RILP simultaneously, enabling formation of the ORP1L-Rab7-RILP tripartite complex. Mutational disruption of the ORP1L-Rab7 interface impairs late endosome positioning. Crystal structure determination, biochemical binding assays, site-directed mutagenesis, late endosome positioning assays The Journal of biological chemistry High 30012887
2019 LRRK1 phosphorylates GTP-bound Rab7 on serine 72 at the endosomal membrane, and this phosphorylation promotes the interaction of Rab7 with RILP, thereby recruiting dynein-dynactin to Rab7-positive vesicles and facilitating dynein-driven transport of EGFR-containing endosomes toward the perinuclear region. Kinase assay, phospho-specific antibodies, co-immunoprecipitation, endosomal transport assays, LRRK1 knockdown Journal of cell science High 31085713
2019 RILP promotes lysosomal degradation of proinsulin by clustering insulin granules and reducing proinsulin-containing granules in pancreatic beta cells. RILP interacts with insulin granule-associated Rab26, restricting insulin secretion. RILP-induced proinsulin degradation is inhibited by lysosomal inhibitors and is Rab7-dependent; RILP depletion sustains proinsulin and increases insulin secretion. Overexpression, RNAi knockdown, lysosomal inhibitor treatment, co-immunoprecipitation with Rab26, insulin secretion assays, islet transplantation Diabetes Medium 31624142
2020 RILP is essential for retrograde transport of neuronal autophagosomes and, unexpectedly, for their biogenesis. mTOR inhibition upregulates RILP expression and its localization to autophagosomes. RILP depletion or mutations in LC3-binding LIR motifs strongly decrease autophagosome numbers. RILP also interacts with ATG5 on isolation membranes, precluding premature dynein recruitment. RILP inhibition impedes autophagic turnover and causes p62/sequestosome-1 aggregation. RNAi knockdown, LIR motif mutagenesis, co-immunoprecipitation with ATG5 and LC3, autophagosome counting, mTOR inhibitor treatment, p62 aggregation assay Developmental cell High 32275887
2021 Rab12 interacts with RILP via its switch I and switch II regions at the RILP homology domain (RHD) of one RILP monomer and a C-terminal threonine of the other monomer in a RILP homodimer. Lysine-71 in Rab12 is critical for interaction with RILP-L1 and RILP-L2 but dispensable for RILP binding. Mutational analyses of RILP RHD confirmed its involvement in regulating secretory granule transport. Molecular dynamics simulations, functional mutational analyses, peptide inhibition assays, biochemical binding assays Scientific reports Medium 33986343
2023 RILP interacts with Grb10 (growth factor receptor binding protein-10) as identified by co-immunoprecipitation, and through this interaction restrains PI3K/AKT/mTOR signaling. RILP overexpression promotes autophagy in osteosarcoma cells in a PI3K/AKT/mTOR-dependent manner; partial attenuation by autophagy inhibitor 3-MA implicates autophagy in EMT regulation. Co-immunoprecipitation, RNA-seq pathway analysis, PI3K activator rescue, 3-MA autophagy inhibition, xenograft mouse model Molecular medicine Medium 37789274
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 then recruits RILP and dynein to lysosomes for retrograde transport. Loss of DENND6A impairs autophagic flux. Cell-based GEF assay screening all Rabs, co-immunoprecipitation, lysosome positioning assays, RNAi knockdown, autophagic flux assays Nature communications Medium 38296963
2024 RILP interacts with ORP1L to competitively inhibit formation of the VAP-ORP1L contact site between the ER and endolysosomes. RILP overexpression causes late endosome/lysosome clustering, reduces ER-endolysosome contact, and leads to cholesterol accumulation in clustered endolysosomes, triggering RILP-dependent cellular autophagy. Co-immunoprecipitation, immunofluorescence microscopy, cholesterol staining, autophagy assays, overexpression studies Cells Medium 39195203
2024 pH neutralization of late endosomes increases assembly of the V1G1 subunit of V-ATPase on endosomal membranes, which stabilizes GTP-bound Rab7 via RILP (a known interactor of both Rab7 and V1G1), causing Rab7 hyperactivation and disrupting late endosomal tubulation and CI-M6PR recycling. LLOMe treatment, NH4Cl pH neutralization, Rab7 hyperactive mutants, immunofluorescence, CI-M6PR trafficking assay Journal of cell science Medium 38578235
2024 Rab7 phosphorylation at Tyrosine 183 in diabetic cardiomyocytes allows recruitment of RILP to promote lysosomal degradation of lipid droplets via microlipophagy. Rab7 activator ML-098 enhanced RILP levels and rescued cardiac dysfunction in diabetic mice. Rab7-CKO mice, RNA-seq, phospho-specific analysis, in vivo Rab7 activator treatment, cardiac function assays Advanced science Low 38837607
2024 HDAC1 (stabilized by deubiquitinase USP5) deacetylates RILP in DDP-resistant NSCLC cells, reducing RILP acetylation levels and contributing to cisplatin resistance. RILP upregulation counteracts the effects of HDAC1 overexpression on cisplatin resistance. Co-immunoprecipitation for USP5-HDAC1 interaction, RILP acetylation co-IP assay, HDAC1/USP5 silencing, MG132 assay, xenograft model Thoracic cancer Low 39582290
2025 RILP functions as a dynein adaptor for late endosome motility in dendrites, dependent on RAB7A binding: expression of RAB7A-L8A (RILP-binding-deficient mutant) impairs retrograde late endosome transport in dendrites and inhibits dendrite arborization. Surprisingly, lysosomal fusion and somatic degradation do not require RAB7A-RILP interaction, separating transport from degradation functions. RILP also promotes endosome carrier formation in dendrites. Separation-of-function RAB7A mutant (L8A) expression in rat/mouse hippocampal neurons, live imaging, dendrite arborization assays, cargo degradation assays bioRxivpreprint Medium bio_10.1101_2025.09.03.673267
2025 RILP cleavage (induced by inflammatory mediators LPS/ATP via caspase-1) impairs tau degradation in microglia, increases intracellular tau accumulation, and enhances cell-cell tau propagation. RILP cleavage status influences extracellular vesicle secretion in microglia. Expression of a noncleavable RILP mitigates inflammation-enhanced tau propagation. LPS/ATP treatment, caspase-1 activation, noncleavable RILP mutant expression, tau propagation assay, EV secretion assay, AD brain tissue analysis Molecular biology of the cell Medium 40137558

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors. Current biology : CB 645 11696325
2009 Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. The Journal of cell biology 564 19564404
2001 Rab-interacting lysosomal protein (RILP): the Rab7 effector required for transport to lysosomes. The EMBO journal 436 11179213
2007 Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin. The Journal of cell biology 384 17283181
2003 Phagosomes fuse with late endosomes and/or lysosomes by extension of membrane protrusions along microtubules: role of Rab7 and RILP. Molecular and cellular biology 351 12944476
2013 Late endosomal transport and tethering are coupled processes controlled by RILP and the cholesterol sensor ORP1L. Journal of cell science 165 23729732
2004 Salmonella impairs RILP recruitment to Rab7 during maturation of invasion vacuoles. Molecular biology of the cell 130 15121880
2007 RILP is required for the proper morphology and function of late endosomes. Journal of cell science 97 17959629
2008 Huntingtin regulates RE1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) nuclear trafficking indirectly through a complex with REST/NRSF-interacting LIM domain protein (RILP) and dynactin p150 Glued. The Journal of biological chemistry 87 18922795
2016 Folliculin directs the formation of a Rab34-RILP complex to control the nutrient-dependent dynamic distribution of lysosomes. EMBO reports 79 27113757
2012 The Rab interacting lysosomal protein (RILP) homology domain functions as a novel effector domain for small GTPase Rab36: Rab36 regulates retrograde melanosome transport in melanocytes. The Journal of biological chemistry 75 22740695
2017 Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A. The Journal of biological chemistry 70 28465352
2007 Mycobacterium bovis BCG disrupts the interaction of Rab7 with RILP contributing to inhibition of phagosome maturation. Journal of leukocyte biology 67 18040083
2014 RILP regulates vacuolar ATPase through interaction with the V1G1 subunit. Journal of cell science 65 24762812
2020 The Dynein Adaptor RILP Controls Neuronal Autophagosome Biogenesis, Transport, and Clearance. Developmental cell 57 32275887
2012 Melanoregulin regulates retrograde melanosome transport through interaction with the RILP-p150Glued complex in melanocytes. Journal of cell science 53 22275436
2012 The Rilp-like proteins Rilpl1 and Rilpl2 regulate ciliary membrane content. Molecular biology of the cell 52 23264467
2006 RILP interacts with VPS22 and VPS36 of ESCRT-II and regulates their membrane recruitment. Biochemical and biophysical research communications 49 17010938
2003 A unique region of RILP distinguishes it from its related proteins in its regulation of lysosomal morphology and interaction with Rab7 and Rab34. Molecular biology of the cell 47 14668488
2006 Characterization of the REST/NRSF-interacting LIM domain protein (RILP): localization and interaction with REST/NRSF. Journal of neurochemistry 45 16417580
2006 RILP interacts with the VPS22 component of the ESCRT-II complex. Biochemical and biophysical research communications 43 16857164
2019 LRRK1 phosphorylation of Rab7 at S72 links trafficking of EGFR-containing endosomes to its effector RILP. Journal of cell science 42 31085713
2019 RILP Restricts Insulin Secretion Through Mediating Lysosomal Degradation of Proinsulin. Diabetes 38 31624142
2010 IGF-I stimulates Rab7-RILP interaction during neuronal autophagy. Neuroscience letters 37 20849920
2016 Hepatitis C virus promotes virion secretion through cleavage of the Rab7 adaptor protein RILP. Proceedings of the National Academy of Sciences of the United States of America 35 27791088
2016 Rab12 Regulates Retrograde Transport of Mast Cell Secretory Granules by Interacting with the RILP-Dynein Complex. Journal of immunology (Baltimore, Md. : 1950) 34 26740112
2024 Targeting Rab7-Rilp Mediated Microlipophagy Alleviates Lipid Toxicity in Diabetic Cardiomyopathy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 29 38837607
2018 A non-canonical GTPase interaction enables ORP1L-Rab7-RILP complex formation and late endosome positioning. The Journal of biological chemistry 28 30012887
2009 Thiazolidinediones induce Rab7-RILP-MAPK-dependent juxtanuclear lysosome aggregation and reduce tumor cell invasion. Traffic (Copenhagen, Denmark) 28 20015112
2014 A new V-ATPase regulatory mechanism mediated by the Rab interacting lysosomal protein (RILP). Communicative & integrative biology 27 26843904
2023 RILP inhibits tumor progression in osteosarcoma via Grb10-mediated inhibition of the PI3K/AKT/mTOR pathway. Molecular medicine (Cambridge, Mass.) 22 37789274
2020 Cln1-mutations suppress Rab7-RILP interaction and impair autophagy contributing to neuropathology in a mouse model of infantile neuronal ceroid lipofuscinosis. Journal of inherited metabolic disease 19 32279353
2015 RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS. Cell death & disease 18 26469971
2009 Detection of activated Rab7 GTPase with an immobilized RILP probe. Methods in molecular biology (Clifton, N.J.) 18 19347311
2024 DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy. Nature communications 17 38296963
2021 Vps34 Inhibits Hepatocellular Carcinoma Invasion by Regulating Endosome-Lysosome Trafficking via Rab7-RILP and Rab11. Cancer research and treatment 16 33781048
2020 Methylation of RILP in lung cancer promotes tumor cell proliferation and invasion. Molecular and cellular biochemistry 14 33128214
2001 Expression analysis and chromosomal assignment of PRA1 and RILP genes. Biochemical and biophysical research communications 14 11520070
2020 A RILP-regulated pathway coordinating autophagosome biogenesis with transport. Autophagy 13 32597306
2018 Caspase-1 regulates cellular trafficking via cleavage of the Rab7 adaptor protein RILP. Biochemical and biophysical research communications 12 30100068
2005 Assay and functional properties of Rab34 interaction with RILP in lysosome morphogenesis. Methods in enzymology 12 16473629
2024 Collapse of late endosomal pH elicits a rapid Rab7 response via the V-ATPase and RILP. Journal of cell science 11 38578235
2017 Characterization of the role of RILP in cell migration. European journal of histochemistry : EJH 10 28735522
2007 Phagosome maturation in unicellular eukaryote Paramecium: the presence of RILP, Rab7 and LAMP-2 homologues. European journal of histochemistry : EJH 10 17921111
2005 Expression, assay, and functional properties of RILP. Methods in enzymology 9 16473628
2015 Quantitative bead-based flow cytometry for assaying Rab7 GTPase interaction with the Rab-interacting lysosomal protein (RILP) effector protein. Methods in molecular biology (Clifton, N.J.) 8 25800855
2023 Disruption of Golgi markers by two RILP-directed shRNAs in neurons: A new role for RILP or a neuron-specific off-target phenotype? The Journal of biological chemistry 5 37315786
2021 Roles of the multivalent dynein adaptors BicD2 and RILP in neurons. Neuroscience letters 5 33667600
2025 RILP cleavage links an inflammatory state to enhanced tau propagation in a cell culture model of Alzheimer's disease. Molecular biology of the cell 4 40137558
2024 USP5-dependent HDAC1 promotes cisplatin resistance and the malignant progression of non-small cell lung cancer by regulating RILP acetylation levels. Thoracic cancer 4 39582290
2023 A Novel Role for RILP in Regulating Osteoclastogenesis and Bone Resorption. Laboratory investigation; a journal of technical methods and pathology 4 36801641
2021 Biochemical and structural insights into Rab12 interactions with RILP and its family members. Scientific reports 4 33986343
2019 Molecular cloning of the Rab7 effector RILP (Rab-interacting lysosomal protein) in Litopenaeus vannamei and preliminary analysis of its role in white spot syndrome virus infection. Fish & shellfish immunology 4 31059814
2025 Mechanism of mTOR/RILP-regulated autophagic flux in increased susceptibility to myocardial ischemia-reperfusion in diabetic mice. Frontiers in pharmacology 3 39958873
2023 Evolutional insights into the interaction between Rab7 and RILP in lysosome motility. iScience 3 37534141
2022 RILP inhibits proliferation, migration, and invasion of PC3 prostate cancer cells. Acta histochemica 3 35981451
2024 RILP Induces Cholesterol Accumulation in Lysosomes by Inhibiting Endoplasmic Reticulum-Endolysosome Interactions. Cells 2 39195203
2024 Collapse of late endosomal pH elicits a rapid Rab7 response via V-ATPase and RILP. bioRxiv : the preprint server for biology 1 37961579
2011 RE1-silencing transcription factor (REST) and REST-interacting LIM domain protein (RILP) affect P19CL6 differentiation. Genes to cells : devoted to molecular & cellular mechanisms 1 21199191
2026 Cepharanthine-mediated PD-L1 autophagic degradation via regulation of TSPO and RILP boosts anti-lung cancer chemo-immunotherapy efficacy. Biochimica et biophysica acta. Molecular basis of disease 0 42191265
2023 "Disruption of Golgi markers by two RILP-directed shRNAs in neurons: a new role for RILP or a neuron-specific off-target phenotype?". bioRxiv : the preprint server for biology 0 36945482
2023 Functional assessment of lysosomal Rab7 and RILP with RNA interference and overexpression in Spodoptera frugiperda Sf9 cell lines. STAR protocols 0 37851568

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