Disease relevance of GOLGA2

• Interaction with GM130 during HERG ion channel trafficking. Disruption by type 2 congenital long QT syndrome mutations. Human Ether-à-go-go-Related Gene [1].
• Confocal microscopy reveals co-localization of alphaB-crystallin with BODIPY TR ceramide and the Golgi matrix protein, GM130, in the perinuclear Golgi in human glioblastoma U373MG cells [2].

High impact information on GOLGA2

• Mitotic fragmentation of the Golgi apparatus can be largely explained by disruption of the interaction between GM130 and the vesicle-docking protein p115 [3].
• Here we identify a single serine (Ser-25) in GM130 as the key phosphorylated target and Cdc2 as the responsible kinase [3].
• MEK1, a component of the MAP kinase signaling pathway recently implicated in mitotic Golgi fragmentation, was not required for GM130 phosphorylation or mitotic fragmentation either in vitro or in vivo [3].
• Cdc2 kinase directly phosphorylates the cis-Golgi matrix protein GM130 and is required for Golgi fragmentation in mitosis [3].
• GRASP65 is complexed with GM130 and is tightly bound to Golgi membranes, even under mitotic conditions when both are heavily phosphorylated [4].

Chemical compound and disease context of GOLGA2

• Using discontinuous sucrose density gradient fractionation of post-nuclear supernatants, prepared from rat tissues and human glioblastoma cell line U373MG, we have identified discrete membrane-bound fractions of alphaB-crystallin, which co-sediment with the Golgi matrix protein, GM130 [2].

Biological context of GOLGA2

• Here, we demonstrate that ribbon formation is mediated by specific membrane-fusion events that occur during Golgi assembly, and require the Golgi proteins GM130 and GRASP65 [5].
• Giantin, GM130, and GalNAcT2 relocated with approximately equal kinetics [6].
• In telophase, GM130 is dephosphorylated as the Golgi fragments start to reassemble [7].
• GM130 is phosphorylated in prophase as the Golgi complex starts to break down, and remains phosphorylated during further breakdown and partitioning of the Golgi fragments in metaphase and anaphase [7].
• YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3zeta [8].

Anatomical context of GOLGA2

• Overexpression of GM130 suppressed HERG current amplitude in Xenopus oocytes, as if by providing an excess of substrate at the Golgi checkpoint [1].
• In rat cardiac myocytes and HEK-293 cells, confocal immunocytochemistry showed co-localization of GM130 and HERG to the Golgi apparatus [1].
• One of the two minor targets of NEM is GM130, previously implicated in the docking of transport vesicles and mitotic fragmentation of the Golgi stack [4].
• Treatment with brefeldin A did not lead to redistribution of LZTR-1 to the endoplasmic reticulum but caused its relocalization in dispersed, punctuated structures that were also positive for GM130 [9].
• These tubular networks are connected to the endoplasmic reticulum, the plasma membrane and the forming polar tube, and are positive for Sec13, gammaCOP and analogs of giantin and GM130 [10].

Associations of GOLGA2 with chemical compounds

• In addition, GM130 binding activates these kinases by promoting autophosphorylation of a conserved threonine within the T-loop [8].
• GM130 was not re-distributed to the ER in the presence of brefeldin A but maintained its overlap with syntaxin5 and a partial overlap with the ER-Golgi intermediate compartment marker, p53 [11].
• When cells were microinjected with Sar1pWT DNA to reverse a guanosine 5'-diphosphate-restricted Sar1p endoplasmic reticulum-exit block phenotype, GM130 and p27 collected perinuclearly with little to no exit of a cisternal enzyme from the endoplasmic reticulum [12].
• The toxic and mutagenic effects of the alkylating agents methylnitrosourea (MNU) and methylnitronitrosoguanidine (MNNG) and of the frameshift mutagen, ICR-191 were compared among 3 human diploid lymphoblast lines, MIT-2, WI-L2 and GM 130 [13].
• The glutathione (GSH) content was shown to increase as cells (GM130, HL60, U937) progressed through the cell cycle [14].

Physical interactions of GOLGA2

• Native GM130 and stably expressed HERG were co-immunoprecipitated from HEK-293 cells using GM130 antibodies [1].
• PIGEA-14 also interacts with GM130, a protein associated with the Golgi matrix, and may therefore represent one important component of the trafficking machinery for polycystin-2 [15].
• The vesicle docking protein p115 binds GM130, a cis-Golgi matrix protein, in a mitotically regulated manner [16].
• These results question a simple tethering model involving a ternary giantin-p115-GM130 complex and suggest that p115-giantin and p115-GM130 interactions might mediate independent membrane tethering events [17].

Other interactions of GOLGA2

• In this process, p115, another coiled-coil protein, is though to bind to giantin on vesicles and to GM130 on cisternae, thus acting as a tether holding the two together [12] [13] [18].
• We propose that the cytoplasmic C terminus of HERG participates in the tethering or possibly targeting of HERG-containing vesicles within the Golgi via its interaction with GM130 [1].
• Interestingly, we also show that Iporin interacts with another rab1 interacting partner, the GM130 protein [19].
• Features of the cDNA suggested that SY11 was a full-length clone encoding golgin-95 but SY2 and SY10 together encoded a partial sequence of golgin-160 [20].
• Cryo-electron microscopy revealed that GRASP65, like GM130, is present on the cis-Golgi, while GRASP55 is on the medial-Golgi [21].

Analytical, diagnostic and therapeutic context of GOLGA2

• Sequence analysis demonstrated that golgin-95 and golgin-160 share 43% sequence similarity and, therefore, may be functionally related proteins [20].
• A GST-rab33b fusion protein stabilised in its GTP form was found to interact by Western blotting or mass spectroscopy with Golgi protein GM130 and rabaptin-5 and rabex-5, two rab effector molecules thought to function exclusively in the endocytic pathway [22].
• Gel filtration revealed that GRASP65 and GM130 interact in detergent extracts of Golgi membranes under both interphase and mitotic conditions, and that this complex can bind to the vesicle docking protein p115 [23].
• Immunoelectron microscopy confirmed this location showing that most of the GM130 was located in the CGN and in one or two cisternae on the cis-side of the Golgi stack [11].
• Instead, double immunofluorescence demonstrated that TNSALP (N153D) partially co-localized with a cis-Golgi marker (GM-130) at the steady-state [24].

References