Disease relevance of GOLGA4

• In immunofluorescence and electron microscopy of cultured fibroblasts, as well as of various other cells (endothelial, epithelial, lenticular, monocytes, neuroblastoma cells) and tissues (human kidney and liver), p230 was localized as a distinct subplasmalemmal layer in the peripheral cytoplasm of the cells [1].
• Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein [2].
• When Matrigel fragments containing these bcr-abl+ cells were implanted subcutaneously in SCID or Balb-C mice they became significantly more vascularized and hemoglobinized than implants containing normal or wt cells (p185 > p210 > p230) [3].
• p230 does not always predict a mild clinical course in myeloid malignancies: e19a2 bcr/abl fusion transcript with additional chromosome abnormalities in a patient with acute monoblastic leukemia (M5a) [4].
• Novel variant of p230 trans-Golgi network protein identified by serum from Sjögren's syndrome patient [5].

High impact information on GOLGA4

• The structure is consistent with golgin-245 forming parallel coiled-coils and suggests how Arl1-GTP/GRIP complexes interact with Golgi membranes via the N termini of Arl1-GTP and the C-terminal tails of the GRIP domains [6].
• Only the acrosomal cap and the principal piece of the tail were decorated with rabbit and hydridoma antibodies against an immunoanalogue of erythrocyte alpha-spectrin (p230). p230 appeared to be the major calmodulin-binding polypeptide in spermatozoa, as shown by a direct overlay assay of electrophoretic blots of spermatozoa with 125I-calmodulin [7].
• The p36 substrate of tyrosine-specific protein kinases co-localizes with non-erythrocyte alpha-spectrin antigen, p230, in surface lamina of cultured fibroblasts [8].
• Upon demecolcine-induced reorganization of intermediate filaments, however, the localization of p230 was rapidly altered to a dense plaque underneath the perinuclear aggregate of intermediate filaments [1].
• We have used here polyclonal antisera and monoclonal antibodies in indirect immunofluorescence microscopy to study the subcellular location of p36 and the p230, which is a subplasmalemmal polypeptide showing immunologic cross-reactivity with erythrocyte alpha-spectrin [8].

Biological context of GOLGA4

• Collectively these results show that GCC88, GCC185 and p230/golgin245 are recruited to functionally distinct domains of the TGN and are likely to be important for the maintenance of TGN subdomain structure, a critical feature for mediating protein sorting and membrane transport [9].
• To identify molecules that interact with the flexible amino-terminal end of p230, we used this domain as bait to screen a human brain cDNA library in a yeast two-hybrid assay [10].
• Molecular characterization of trans-Golgi p230. A human peripheral membrane protein encoded by a gene on chromosome 6p12-22 contains extensive coiled-coil alpha-helical domains and a granin motif [11].
• The role of G protein activators on the binding of p230 to Golgi membranes and in vesicle biogenesis has been investigated [12].
• By analyzing more than 30 mutants of golgin-97 and golgin-245 GRIP domains for their properties of dimerization, interaction with ARF like protein 1 (Arl1)-GTP and Golgi targeting, we found hierarchically organized three-tier interactions governing the Golgi targeting of GRIP domain golgins [13].

Anatomical context of GOLGA4

• Previously, using human autoimmune sera, we identified and characterized a TGN protein, p230/Golgin-245, an extensively coiled-coil protein with flexible amino- and carboxyl-terminal ends, that is anchored to TGN membranes and TGN-derived vesicles by its carboxyl-terminal GRIP domain [10].
• Previously, we have identified a carboxy-terminal domain of the trans-Golgi-network (TGN) protein p230 that is responsible for Golgi localisation [1] [14].
• Molecular characterization of Golgin-245, a novel Golgi complex protein containing a granin signature [15].
• We have previously described a brefeldin-A sensitive, hydrophilic protein (p230), containing a very high frequency of heptad repeats, found in the cytosol and associated with Golgi membranes [12].
• Treatment of streptolysin-O permeabilised HeLa cells with either GTP gamma S or AlF4- resulted in accumulation of p230 on Golgi membranes [12].

Associations of GOLGA4 with chemical compounds

• Interaction between p230 and MACF1 is associated with transport of a glycosyl phosphatidyl inositol-anchored protein from the Golgi to the cell periphery [10].
• Giant vacuole formation, of confirmed trans-Golgi origin (labeled with C5-ceramide, p230, golgin-97), is a cellular response to all tested amines in the series (> or = 2.5 mM), including triethylamine [16].
• Both p36 and p230 showed a diffuse distribution in fixed and permeabilized cells and were localized in a surface lamina-like network in Triton-extracted cells [8].
• The alternative splicing occurs within the first proline-rich domain of p230 [5].

Regulatory relationships of GOLGA4

• Endogenous p230 was displaced from the Golgi membranes in transfected cells expressing high levels of GFP fused to the GLD of either p230 or golgin-97, indicating that different GLDs interact with similar membrane determinants [14].

Other interactions of GOLGA4

• Arl1-GTP thus functions to recruit Golgin-97 and Golgin-245 onto the Golgi via interacting with their GRIP domains [17].
• Golgin-97 and Golgin-245 are dissociated from the Golgi when Arl1 is knocked-down by its siRNA [17].
• The DNA sequence results of an about 685-kb region indicated that the size of the homozygously deleted segment was 638,489 bp, in which we identified only four genes including the integrin alpha RLC and the trans-Golgi p230 genes, both reported previously [18].
• We show here that p230 is localised on the trans-Golgi network, by immunogold labeling of HeLa cell cryosections using alpha 2,6 sialyltransferase as a compartment-specific marker [12].

Analytical, diagnostic and therapeutic context of GOLGA4

• Here we report the molecular cloning and sequence analysis of human p230 and the localization of its gene to chromosome 6p12 22 [11].
• The e1a2, b2a2 or b3a2 and c3a2 fusion mRNAs encode distinct fusion proteins (p190, p210 and p230, respectively), which are associated with different forms of leukemogenesis in humans and animal models [19].
• RT-PCR analysis indicated that the splicing occurs independently of previously reported carboxyl-terminal splicing, and that this novel splice variant is more frequent than the previously reported p230 [5].
• GFP fusion proteins containing either the T. brucei GRIP domain or the human p230 GRIP (p230GRIP) domain were also expressed in the trypanosomatid parasite, Leishmania mexicana, and localized by fluorescence and immuno-electron microscopy to the trans face of the single Golgi apparatus and a short tubule that extended from the Golgi apparatus [20].

References