Disease relevance of RAB7A

• There are two known autosomal dominant genes for the hereditary ulcero-mutilating neuropathies: SPTLC1 (hereditary sensory neuropathy type 1) and RAB7 (Charcot-Marie-Tooth disease type 2B) [1].
• Overexpression of ORP1L, and in particular the N-terminal fragments of ORP1L, inhibits vacuolation of LE caused by Helicobacter pylori toxin VacA, a process also involving Rab7 [2].
• The Wilson disease protein ATP7B resides in the late endosomes with Rab7 and the Niemann-Pick C1 protein [3].
• This was achieved by expressing the individual components in baculovirus and Escherichia coli systems with subsequent purification followed by in vitro monoprenylation of Rab7 with immobilized recombinant RabGGTase [4].
• We compared the expression level and membrane recruitment of Rab5a and Rab7 in autonomous thyroid adenomas (where the cAMP cascade is constitutively activated) and surrounding quiescent tissues [5].

Psychiatry related information on RAB7A

• PSN was associated with significantly lower scores (i.e., worse quality of life) in the mental health scale; CAD was associated with significant reductions of all but role-emotional and mental health scales of the SF-36; and PVD was associated with significantly lower physical and social functioning scales [6].
• A set of problem solving strategies integrated into nursing process in nursing core courses (PSNP) was developed for students enrolled in a post-RN baccalaureate nursing program (RN-BSN) in a university in Taiwan. The purpose of this study, therefore, was to evaluate the effectiveness of PSNP on students' clinical problem solving abilities [7].

High impact information on RAB7A

• Fusion could be inhibited by cytosol containing the overexpressed mutant rab5lle133, which does not bind GTP on blots, and by antibodies against rab5, but not against rab2 or rab7 [8].
• The second, rab5, is located at the cytoplasmic surface of the plasma membrane and on early endosomes, while the third, rab7, is found on late endosomes [9].
• To define the region mediating their specific localization, we transiently expressed rab2, rab5 and rab7 hybrid proteins in BHK cells, and determined their intracellular localization by immunofluorescence confocal microscopy and subcellular fractionation [10].
• A role for rab7 GTPase in growth factor-regulated cell nutrition and apoptosis [11].
• Our results demonstrate a role for Rab7 and Rab9 in the Golgi targeting of glycosphingolipids and suggest a new therapeutic approach for restoring normal lipid trafficking in NP-C cells [12].

Chemical compound and disease context of RAB7A

• When NO-catalyzed degradation of HS was depressed in mouse neuroblastoma cell line (N2a) by using 3-beta[2(diethylamino) ethoxy]androst-5-en-17-one (U18666A), both ascorbate and dehydroascorbic acid restored formation of anMan-positive products that colocalized with Rab7 [13].

Biological context of RAB7A

• The alignment of RAB7 orthologs shows that both missense mutations target highly conserved amino acid residues [14].
• NotI linking/jumping clones of human chromosome 3: mapping of the TFRC, RAB7 and HAUSP genes to regions rearranged in leukemia and deleted in solid tumors [15].
• Rab7: a key to lysosome biogenesis [16].
• Taken together, these in vivo and in vitro observations demonstrate that thyroid-stimulating hormone, via cAMP, coordinately enhances the expression of Rab5a and Rab7, which promote Tg endocytosis and transfer to lysosomes, respectively, resulting in accelerated thyroid hormone production [5].
• CMT2B maps to chromosome 3q13-q22 [14].

Anatomical context of RAB7A

• RAB7 is ubiquitously expressed, and we found expression in sensory and motor neurons [14].
• Recently two genes, RAB38 and RAB7, were reported to play an important role in melanogenesis in the melanocyte, suggesting that these two genes could be good candidates for new OCA loci [17].
• RILP-C33 (a truncated form of the protein lacking the N-terminal half) strongly inhibits epidermal growth factor and low-density lipoprotein degradation, and causes dispersion of lysosomes similarly to Rab7 dominant-negative mutants [18].
• Furthermore, when inhibitory mutants of rab7 are expressed, the internalized EGF.EGFR complex accumulates in high-density endosomes that are characteristic of the late endocytic pathway [19].
• We have now used a new approach to analyze the role of Rab7: transient expression of Enhanced Green Fluorescent Protein (EGFP)-tagged Rab7 wt and mutant proteins in HeLa cells [16].

Associations of RAB7A with chemical compounds

• Sequencing the RAB7 gene showed a novel heterozygous A to C mutation, changing asparagine to threonine at codon 161 [1].
• The mutation is situated adjacent to a previously identified valine to methionine mutation at codon 162, implying a hotspot for mutations in the highly conserved C terminus of RAB7 [1].
• The endocytic catalysts, Rab5a and Rab7, are tandem regulators of thyroid hormone production [5].
• This could also be overcome by the addition of ascorbate, which induced formation of anMan-positive degradation products that colocalized with Rab7 [13].
• Rab5 and Rab7 Control Endocytic Sorting along the Axonal Retrograde Transport Pathway [20].

Physical interactions of RAB7A

• The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments [2].
• Crystallization and preliminary X-ray diffraction analysis of monoprenylated Rab7 GTPase in complex with Rab escort protein 1 [21].
• Indeed, RILP induces recruitment of dynein-dynactin motor complexes to Rab7-containing late endosomes and lysosomes [22].
• The Rab7-binding determinant is mapped to the ankyrin repeat (ANK) region of ORP1L [2].
• Rab7 is required for late endosomal transport and here we establish that the phosphatidylinositol 3'-kinase hVPS34 and its adaptor protein p150 are rab7 interacting partners [23].

Co-localisations of RAB7A

• GFP-ATP7B colocalized with various late endosome markers including Rab7 and NPC1 but not with Golgi or lysosome markers [3].
• The hVPS34/p150 complex colocalized with rab7 on late endosomes and hVPS34 activity was dependent on nucleotide cycling of rab7 [23].

Regulatory relationships of RAB7A

• We propose that the departure of SNX5-positive tubules represents a rapid mechanism of recycling components from macropinosomes thereby promoting their maturation into Rab7-positive structures [24].
• RILP has a key role in the control of transport to degradative compartments together with Rab7 and probably links Rab7 function to the cytoskeleton [25].

Other interactions of RAB7A

• All these data are consistent with a model in which RILP represents a downstream effector for Rab7 and both proteins act together in the regulation of late endocytic traffic [18].
• In contrast, after ingestion, dead bacteria colocalized with late endosome marker Rab7, and lysosome markers LAMP1 and cathepsin D, but not with calnexin or MDC [26].
• Staphylococci-containing phagosomes were matured by sequential and dynamic interactions with Rab5- and Rab7-positive vesicles [27].
• Characterization of the human RAB38 and RAB7 genes: exclusion of new major pathological loci for Japanese OCA [17].
• ORP1L localizes to late endosomes (LEs)/lysosomes, colocalizing with the GTPases Rab7 and Rab9 and lysosome-associated membrane protein-1 [2].

Analytical, diagnostic and therapeutic context of RAB7A

• Charcot-Marie-Tooth type 2B (CMT2B) is clinically characterized by marked distal muscle weakness and wasting and a high frequency of foot ulcers, infections, and amputations of the toes because of recurrent infections [14].
• Confocal immunofluorescence microscopy showed that the early endosomal GTPases Rab4 and Rab5 both do not codistribute with Rab7 within the same cell [28].
• In this work we have used a combination of organic synthesis and in vitro protein ligation to construct monoprenylated Rab7 GTPase [29].
• Rab7 and Lamp-1, markers for late endosome and late endosome/lysosome, respectively, were subsequently recruited on the ECVs, which was confirmed with flow cytometry analysis of ECVs [30].
• Co-immunoprecipitation, COS cell two-hybrid, and pull-down assays were applied to demonstrate a physical interaction between ORP1L and the late endosomal small GTPase Rab7 [31].

References