HGNC Approved Gene Symbol: RILP
Cytogenetic location: 17p13.3 Genomic coordinates (GRCh38): 17:1,646,150-1,649,866 (from NCBI)
RILP, along with the GTPase RAB7 (602298), controls late endocytic transport (Cantalupo et al., 2001).
Using Rab7 as bait in a yeast 2-hybrid screen, followed by screening a HeLa cell cDNA library, Cantalupo et al. (2001) cloned a full-length RILP cDNA. The deduced 401-amino acid protein has a calculated molecular mass of about 45 kD and contains 2 coiled-coil regions. RILP shares significant homology with a mouse protein belonging to the ezrin (123900)-radixin (179410)-moesin (309845) (ERM) family. Northern blot analysis detected transcripts of about 1.2 and 1.8 kb in the 3 tissues tested (lung, spleen, and stomach). Western blot analysis detected a 50-kD RILP protein in all cell lines examined. Immunolocalization colocalized RILP with several late endosomal/lysosomal marker proteins.
By RNA dot blot analysis, Bucci et al. (2001) determined that RILP is expressed at varying levels in all tissues examined. Expression was highest in adult heart, stomach, adrenal gland, thyroid gland, salivary gland, liver, and lung, and in fetal heart and liver. Expression was lowest in whole fetal brain and in all adult brain regions. Northern blot analysis confirmed ubiquitous expression of 0.9- and 1.8-kb transcripts. Expression levels of the 2 transcripts varied between tissues.
Using PCR, Wang et al. (2004) detected variable RILP expression in all 8 human tissues examined. Database analysis detected orthologs of RILP and RILP-like proteins (RLPs; see 614092) in several multicellular organisms, but not in unicellular organisms. Similarity among the RILP and RLP orthologs was highest in 2 domains that Wang et al. (2004) called RILP homology domain-1 (RH1) and RH2.
Cantalupo et al. (2001) determined that the C-terminal half of RILP interacted with RAB7. It also interacted with a constitutively active GTP-bound RAB7 mutant, but it did not bind an inactive GDP-bound RAB7 mutant or several other RAB proteins. Overexpression of RILP resulted in perinuclear clustering of the late endosomal/lysosomal compartment, which could be reversed by microtubule depolymerization. The perinuclear clustering was similar to that observed in cells expressing wildtype or constitutively active RAB7. Overexpression of the C-terminal half of RILP resulted in lysosome dispersal and inhibition of lysosomal substrate degradation, similar to that observed in cells expressing the inactive GDP-bound RAB7 mutant. Overexpression of RILP was able to prevent or reverse the effects of the inactive RAB7 mutant, leading Cantalupo et al. (2001) to hypothesize that RILP lies downstream of RAB7 in the regulation of late endocytic traffic.
Wang et al. (2004) found that overexpression of human RILP in normal rat kidney cells caused enlargement and relocalization of lysosomes. Experiments with chimeric proteins made up of sequences from RILP and RLP1 (RILPL1; 614092) revealed a 62-amino acid domain in RILP that was necessary to regulate lysosome morphology. The ability to regulate lysosomes correlated with the ability of the chimeric protein to interact with GTP-bound RAB7 or both GTP-bound RAB7 and RAB34 (610917) simultaneously, but not GTP-bound RAB34 alone.
By radiation hybrid analysis, Bucci et al. (2001) mapped the RILP gene to chromosome 17p13.3. Cantalupo et al. (2001) mapped the mouse Rilp gene to chromosome 11.
Bucci, C., De Gregorio, L., Bruni, C. B. Expression analysis and chromosomal assignment of PRA1 and RILP genes. Biochem. Biophys. Res. Commun. 286: 815-819, 2001. [PubMed: 11520070] [Full Text: https://doi.org/10.1006/bbrc.2001.5466]
Cantalupo, G., Alifano, P., Roberti, V., Bruni, C. B., Bucci, C. Rab-interacting lysosomal protein (RILP): the Rab7 effector required for transport to lysosomes. EMBO J. 20: 683-693, 2001. [PubMed: 11179213] [Full Text: https://doi.org/10.1093/emboj/20.4.683]
Wang, T., Wong, K. K., Hong, W. A unique region of RILP distinguishes it from its related proteins in its regulation of lysosomal morphology and interaction with Rab7 and Rab34. Molec. Biol. Cell 15: 815-826, 2004. [PubMed: 14668488] [Full Text: https://doi.org/10.1091/mbc.e03-06-0413]