Disease relevance of TGOLN2

• In contrast, the failure of the QKTT motif and TGN46 cytoplasmic tail to induce steady-state ER localization of vesicular stomatitis virus glycoprotein (VSVG) chimeras in HeLa and NRK cells indicates that significant differences in early secretory trafficking also exist [1].
• We show here that gE/gI and a second glycoprotein, gB, TGN46, and another cellular protein, carboxypeptidase D, all moved to cell junctions after infection with an HSV mutant unable to produce cytoplasmic capsids [2].
• The Menkes disease ATPase (MNK) is a copper transporter that localizes to the mammalian trans-Golgi network (TGN) and shows substantial co-localization wih a ubiquitous TGN resident protein and marker, TGN46 [3].

High impact information on TGOLN2

• TGN38/41 is a heterodimeric integral membrane protein that cycles between the trans Golgi network and the cell surface [4].
• Overexpression of Rab11wt, Rab11Q70L, and Rab11S25N also inhibited STxB and TGN38 transport from endosomes to the TGN [5].
• We also studied transport from endosomes to the Golgi apparatus using the Shiga toxin B subunit (STxB) and TGN38 as reporter molecules [5].
• Overexpression of both Rab11 wild-type (Rab11wt) and mutants altered the localization of the transferrrin receptor (TfR), internalized Tf, the STxB, and TGN38 [5].
• Mutational analysis revealed that Asp176 and Trp421 of mu2 are involved in the interaction with internalization motifs of TGN38 and epidermal growth factor (EGF) receptor [6].

Biological context of TGOLN2

• Moreover, reverse transcription-polymerase chain reaction analysis of hTGN46 transcripts and genomic analysis of a cDNA deposited as an expressed sequence tag in dbEST Data Base revealed that additional cDNAs exist that are produced by alternate usage of 3'-splice sites of intron III [7].
• Whereas rat TGN38 contains 6 tandem repeats of an 8mer, both primate proteins possess 14 tandem repeats of a 14mer sequence [8].
• Direct interaction of the trans-Golgi network membrane protein, TGN38, with the F-actin binding protein, neurabin [9].
• After arrest of the biosynthetic protein transport at 20 degrees C, fluorescent hCgB-GFP colocalized with TGN38, a marker of the TGN [10].
• We have undertaken a series of experiments designed to address this hypothesis, and, in so doing, have partially characterised the glycosylation status of the lumenal domain of TGN38 [11].

Anatomical context of TGOLN2

• The human protein, like rat TGN38, is localised primarily to the TGN but is present on the cell surface and returns via endosomes [8].
• TGN38 is a type I integral membrane protein that constitutively cycles between the trans-Golgi network (TGN) and plasma membrane [9].
• In the present study we expressed chimeric constructs of rat TGN38 and rat lgp120 in HeLa cells [12].
• These data suggest that neurabin provides a direct physical link between TGN38-containing membranes and the actin cytoskeleton [9].
• The lumenal and cytosolic domains of lgp120 contribute to sorting and delivery to lysosomes, whereas the transmembrane and cytosolic domains of TGN38 contribute to sorting and delivery to the trans-Golgi network [12].

Associations of TGOLN2 with chemical compounds

• We have used a combination of yeast two-hybrid and in vitro protein interaction assays to show that this interaction is dependent on the serine (but not tyrosine) residue of the known TGN38 trafficking motif [9].
• Specificity of interaction between adaptor-complex medium chains and the tyrosine-based sorting motifs of TGN38 and lgp120 [13].
• Under physiological conditions when TGN38 is not overexpressed, it interacts with integrin beta 1 [14].
• The luminal domain of TGN38 interacts with integrin beta 1 and is involved in its trafficking [14].
• The TGN38 glycoprotein contains two non-overlapping signals that mediate localization to the trans-Golgi network [15].

Physical interactions of TGOLN2

• Confocal analysis revealed that these vesicles were devoid of TGN38 and of Texas Red-coupled transferrin and cathepsin D, markers of the endosomal/lysosomal pathway [10].

Co-localisations of TGOLN2

• Unexpectedly, in these cells, TGN38 colocalizes with integrin alpha 5 beta 1 at the Golgi, the cell surface or in the footprints and an increased amount of both integrin subunits on the plasma membrane was observed [14].
• Immunoelectron microscopy showed unequivocally that furin resides in the TGN where it colocalized with TGN38 [16].
• Binding to the Golgi was verified by indirect immunofluorescence in MT-1 cells showing that a fraction of profilin I colocalizes with TGN38, a marker of the trans-Golgi network (TGN) [17].

Other interactions of TGOLN2

• Functional analysis reveals that modification of the trafficking of TGN38 results in a parallel change in the distribution of integrin alpha 5 beta 1, leading to the conclusion that TGN38 is involved in the trafficking of integrin beta 1 [14].
• TGN38, which recycles between the TGN and plasma membrane, was transported into and out of the GCC88 decorated structures [18].
• Dual label immunofluorescence demonstrated that in this region, the distribution of PI3K-C2alpha closely paralleled that of gamma-adaptin, a component of the AP-1 adaptor that is present in the trans-Golgi and the trans-Golgi network (TGN) resident protein TGN-46 [19].
• These GCC185-labelled structures included the TGN resident protein alpha2,6 sialyltransferase and excluded the recycling TGN protein, TGN46 [20].
• In nonpolarized cells, AQP2 vesicles were scattered in the cytoplasm and did not colocalize with Golgi 58K or TGN38 [21].

Analytical, diagnostic and therapeutic context of TGOLN2

• This was demonstrated by reciprocal co-immunoprecipitation of integrin beta 1 and TGN38 [14].
• BFA treatment for 12 h also resulted in complete loss of transcobalamin II receptor (TC II-R) activity/protein levels in the BLM and the disappearance of trans-Golgi network (TGN) morphology as revealed by confocal immunofluorescence microscopy using antibody to TGN 38 [22].
• Electron microscopy analyses of GRIP domain-overexpressing cells revealed distended perinuclear vacuoles and a proliferation of multivesicular late endosomes to which the TGN resident protein TGN46 was largely mislocalized [23].
• Indirect immunofluorescence of cells infected with chlamydiae stained with an antibody to the trans-Golgi network (TGN) protein TGN38 demonstrated that in infected cells, the integrity and structure of the TGN was altered [24].
• TGN38 cycles to the plasma membrane and back, which is shown by addition of TGN38 luminal domain antibodies directly to cell culture media [25].

References