Disease relevance of RAB1A

• Aberrant expression of RAB1A in human tongue cancer [1].
• We show that rab1 is an excellent marker of the intermediate compartment, and we use this marker, as well as budding profiles of the mouse hepatitis virus (MHV) in cells infected with this virus, to identify this compartment [2].
• The cells were also tested for the FMC7, defined previously on PLL cells and the RAB1, a newly described hairy cell leukemia antigen [3].
• These results indicate that increased expression of Rab1 GTPase in myocardium distorts subcellular localization of proteins and is sufficient to cause cardiac hypertrophy and failure [4].

High impact information on RAB1A

• We identify protein partners for TIR-1 and show that the small GTPase Rab1 and the f subunit of ATP synthase participate specifically in the control of antimicrobial peptide gene expression [5].
• Golgin-84 binds to active rab1 but not cis-Golgi matrix proteins [6].
• A GDP-bound of rab1 inhibits protein export from the endoplasmic reticulum and transport between Golgi compartments [7].
• The mutant protein required posttranslational isoprenylation for inhibition and behaved as a competitive inhibitor of wild-type rab1 function [7].
• Hydroxymethylglutaryl-CoA reductase, the key enzyme of cholesterol biosynthesis, colocalized with slowly sedimenting, Rab1-enriched membranes when the IC subdomains were separated by velocity sedimentation [8].

Biological context of RAB1A

• We mapped AHY1.1 and thus human RAB1 on Chr 2p13.4-p14 using somatic cell hybrids and a radiation hybrid panel, thus extending a known region of conserved synteny between mouse Chr 11 and human Chr 2p [9].
• This issue was addressed by determining the role of Rab1, a Ras-related small GTPase that coordinates vesicular protein transport in the early secretory pathway, in the subcellular distribution and function of the angiotensin II type 1A receptor (AT1R), beta2-adrenergic receptor (AR), and alpha2B-AR in HEK293T cells [10].
• The rab1 and rab2 proteins lack the carboxyl-terminal amino acid motif common to all previously identified isoprenylated proteins, i.e. CXXX, where X is an unspecified amino acid [11].
• We have now used these markers to construct a 1.3-Mb yeast artificial chromosome (YAC) contig of the Rab1 region on mouse Chr 11 [9].
• Nucleotide sequence of a new YPT1-related human cDNA which belongs to the ras gene superfamily [12].

Anatomical context of RAB1A

• We mapped the rab1 interacting domain to the C-terminus of MICAL-1, which also mediates binding to the intermediate filament vimentin [13].
• Together with rab1, these molecules are components of a protein complex, which mediates and regulates intracellular vesicle transport [14].
• GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex [15].
• Differentiation involves expansion of the IC and movement of Rab1-containing tubules to the growth cones of the neurites, whereas p58- and COPI-positive IC elements, like rough ER and Golgi, remain in the cell body [8].
• In combination with cytosol immunodepleted of Rab1, it is seen that alpha-SNAP is required after a Rab1-requiring step [16].

Associations of RAB1A with chemical compounds

• Alpha-SNAP but not gamma-SNAP is required for ER-Golgi transport after vesicle budding and the Rab1-requiring step but before the EGTA-sensitive step [16].
• Regulation of the cell surface expression and function of angiotensin II type 1 receptor by Rab1-mediated endoplasmic reticulum-to-Golgi transport in cardiac myocytes [17].
• Brefeldin A inhibited beta-AR and alpha1-AR export and antagonized the Rab1 effect on alpha1-AR expression [18].
• Consistent with the effects on receptor cell-surface targeting, Rab1 selectively enhanced ERK1/2 activation and hypertrophic growth in response to the alpha1-AR agonist phenylephrine but not to the beta-AR agonist isoproterenol [18].
• SidM is a guanosine nucleotide exchange factor for Rab1 that recruits Rab1 to Legionella-containing vacuoles, a process that is enhanced by LidA [19].

Regulatory relationships of RAB1A

• These data indicate that Rab1 GTPase selectively regulates intracellular trafficking and signaling of G protein-coupled receptors and suggest a novel, as yet undefined pathway for movement of G protein-coupled receptors from the ER to the cell surface [10].

Other interactions of RAB1A

• MICAL-1 isoforms, novel rab1 interacting proteins [13].
• The rab1, rab2, rab3A, and rab4 proteins are the human counterparts of the rat rab gene products that we have previously characterized [20].
• Cell fractionation revealed that in contrast to the mainly membrane-associated rab1 effector GM130, MICAL-1 displays a predominantly cytosolic localization [13].
• A similar binding was seen to rab1 but not to rab6, both Golgi rabs [21].
• RESULTS: Here, we report the characterization of Iporin, which is similar to KIAA0375 as a novel rab1-interacting protein [14].

Analytical, diagnostic and therapeutic context of RAB1A

• Elevated expression of Rab1, the mammalian YPT1 homolog, protected against alphaSyn-induced dopaminergic neuron loss in animal models of PD [22].
• Using indirect immunofluorescence methods and microscopic or flow cytometric analysis, it was found that the RAB-1 antigen was expressed on few resting B cells and not on resting T lymphocytes, platelets, monocytes, erythroid and myeloid cells [23].

References