Disease relevance of Anxa3

• Expression levels were similar in pancreas, where PAP III mRNA concentration increased within 6 h following induction of pancreatitis, reached maximal levels (> 200 times control values) at 24-48 h, and decreased thereafter [1].

High impact information on Anxa3

• LC3 is present in greater amounts in ductus compared with aorta cells, and overexpression of LC3 in aortic cells by transfection enhances fibronectin mRNA translation to levels observed in ductus cells [2].
• Immunoelectron microscopy on LC3 revealed specific labelling of autophagosome membranes in addition to the cytoplasmic labelling [3].
• The deduced amino acid sequence of LC3 is highly conserved between rat and mouse [4].
• Our anti-LC3 antiserum shows that LC3 is abundant only in neurons and that the majority of LC3 in brain co-purifies with microtubules [4].
• Consistent with this, overexpression of LC3 decreased the level of active GTP-bound Rac1 in COS cells [5].

Biological context of Anxa3

• Interestingly, two binding sites exist in LC3 for caldendrin from which only one exhibits a strict Ca(2+)-dependency for the interaction to take place but both require the presence of the first two EF-hands of caldendrin [6].
• The PAP III coding sequence spanned over six exons [1].
• Moreover, the rat PAP III gene was mapped to chromosome 4 using mouse-rat hybrid cells, a localization which coincides with that of the PAP I and II genes [1].
• The autophagy induced in mitotic cells was inhibited by amino acids, and the resulting autophagosomes contained proteins LC3 and Lamp1, known to be associated with autophagosomes in interphase cells [7].
• The structure of LC3, which is similar to those of Golgi-associated ATPase enhancer of 16 kDa (GATE-16) and GABAA receptor-associated protein (GABARAP), contains a ubiquitin core with two alpha helices, alpha1 and alpha2, attached at its N-terminus [8].

Anatomical context of Anxa3

• Annexin III is expressed by most sensory neurons, regardless of size, by endothelial cells lining the blood vessels, and by the perineurium [9].
• In the SC, annexin III is primarily expressed by astrocytes [9].
• In transient transfection assays we found that both proteins were primarily localized to the perinuclear region and also scattered throughout the cytosol as dots, a subset of which colocalized with an autophagosome-specific marker LC3 under starvation conditions [10].
• In situ hybridization indicated that PAP-III mRNA expression was limited mainly to the hilar region of the ovarian stroma, with most of the signal emanating from endothelial cells that lined the inner walls of blood vessels, and from small secondary follicles [11].
• Induced expressions of Rab24 GTPase and LC3 in nerve-injured motor neurons [12].

Associations of Anxa3 with chemical compounds

• While Sos1 stimulated the guanine nucleotide exchange reaction on Rac1, LC3 suppressed the ability of Sos1 to activate Rac1 in in vitro experiments using COS cell lysates [5].
• Treatment of the animals with ovulation-blocking doses of indomethacin (an inhibitor of prostanoid synthesis) or epostane (an inhibitor of progesterone synthesis) revealed that ovarian transcription of PAP-III mRNA was moderately dependent on ovarian progesterone synthesis [11].
• By Western blot analysis, we investigated posttranslational modification of LC3 in cultured cells with a high concentration of chloroquine, and found that the autophagosome membrane-bound form of LC3 increased dose-dependently [13].

Other interactions of Anxa3

• In the intestinal tract, where PAP II is not expressed, the pattern of PAP III expression was comparable with that of PAP I; fasting induced a decrease in its mRNA concentration by more than 80%, which could be reversed within 6 h upon feeding [1].
• PAP III belongs to the family of pancreatitis-associated proteins, recently characterized as pancreatic secretory proteins structurally related to C-type lectins, and whose expression is induced during the acute phase of pancreatitis [1].

Analytical, diagnostic and therapeutic context of Anxa3

• Furthermore, LC3 was colocalized with Sos1 in cells, as determined by immunohistochemistry [5].
• LC3 protein expression measured by quantitiative immunoblotting is twice as high in postnatal brain as in embryonic and adult brain [14].
• A polyclonal antibody was raised against PAP III, and a Western blotting analysis using this antibody confirmed an increased level of PAP III protein in the injured nerve [15].
• The RNA extracts were used for RT-PCR differential display to detect PAP-III gene expression in the stimulated ovarian tissue [11].
• The molecular form of LC3 was mainly LC3-II, a membrane-bound form, during reperfusion, especially at 30 min of the phase [16].

References