Disease relevance of RAB34

• Active RAH GzmB expressed in glioblastoma cell lines displayed proteolytic activity, but in contrast to QPY GzmB, it did not accumulate in the nucleus and was unable to induce Bid cleavage, cytochrome c release, or apoptosis [1].

High impact information on RAB34

• In CD8(+) cytotoxic T lymphocytes, GzmB was expressed at similar levels in QPY homozygous, QPY/RAH heterozygous, and RAH homozygous individuals, demonstrating that RAH GzmB is a stable protein [1].
• In coexpression studies, PipB2 can overcome the effects of dominant-active Rab7 or Rab34 on LE/Lys positioning [2].
• A unique region of RILP distinguishes it from its related proteins in its regulation of lysosomal morphology and interaction with Rab7 and Rab34 [3].
• The RAH allele is the first documented variant of the human GrB gene, occurs at a frequency of 25-30%, and encodes three amino acid substitutions (Q48R, P88A, and Y245H) [4].
• Expression of wild-type or GTP-restricted but not GDP-restricted versions of Rab34 causes spatial redistribution of lysosomes from the periphery to the peri-Golgi region [5].

Biological context of RAB34

• Full-length Rab34 was specifically isolated from a human kidney cDNA library [6].
• By using FITC-BSA as an endocytic tracer, we show that Rab39 can facilitate endocytosis in HeLa cells when expressed either transiently or stably [7].
• Full-length cDNA of Rab39 contains 1251bp with an open reading frame (ORF) of 636bp, which is predicted to encode a 211 aa protein [7].
• Assay and functional properties of Rab34 interaction with RILP in lysosome morphogenesis [8].
• The regulation of lysosomal positioning by Rab34 depends on its association with the membrane mediated by prenylation and its direct interaction with Rab-interacting lysosomal protein (RILP) [5].

Anatomical context of RAB34

• Because Rab34 is known to regulate intracellular lysosome positioning, we propose that hmunc13 serves as an effector of Rab34, mediating lysosome-Golgi trafficking [6].
• Rab39 contains conserved motifs involved in phosphate/guanosine binding and a microbody C-terminal targeting signal [7].
• Confocal microscopy examination of Rab39 subcellular localization suggests that Rab39 is associated with Golgi-associated organelles [7].
• RT-PCR analysis indicates that Rab39 is mainly detected in epithelial cell lines, and Northern blot analysis shows that Rab39 is expressed ubiquitously in human tissues [7].
• RILP is emerging as a key regulator of late endocytic pathway by functioning as a downstream effector of activated Rab7 and Rab34, while ESCRT-I-->ESCRT-II-->ESCRT-III machinery acts in sorting proteins to the multivesicular body (MVB) initiated at the early/sorting endosome [9].

Associations of RAB34 with chemical compounds

• Here we report a new high capacity battery system referred to as RAH batteries, which is based upon a high energy cathode-halogen (such as Br(2) or Cl(2)) and metal hydride anode [10].
• SETTING: Clinical Human Research Laboratory, Department of Medicine, RAH, Adelaide, Australia. PARTICIPANTS: Twelve older (5 male/7 female) (age 65-84) and 12 young (5 male/7 female) (age 20-26) healthy subjects [11].
• The modification consisted of following two changes: use of Gill's Haematoxylin instead of RAH and omission of Orange G from cytostain [12].

Physical interactions of RAB34

• Both GST pull-down experiments and direct binding assays in vitro demonstrate that RILP interacts selectively with the wild-type and GTP-restricted but not GDP-restricted form of Rab34 [8].

Regulatory relationships of RAB34

• Expression of EGFP-tagged Rab34 wild-type or GTP-restricted forms in mammalian cells results in redistribution of clustered lysosomes to the peri-Golgi region and this property depends on K82, suggesting that Rab34 regulates lysosome distribution via interaction with RILP [8].

Other interactions of RAB34

• Deletion of munc homolgy domain (MHD)-2, eliminated the hmunc13/Rab34 interaction [6].
• Rabbit polyclonal antibody raised against recombinant Rab34 reveals that Rab34 is a 29-kDa protein present both in the cytosol and in the Golgi apparatus [8].

References