Disease relevance of Anxa7

• Annexin VII-specific polypeptides expressed in Escherichia coli were used to generate isoform-specific monoclonal antibodies [1].
• However, the viable heterozygous Anx7 (+/-) mouse displays a complex phenotype that includes adrenal gland hypertrophy, chromaffin cell hyperplasia, and defective IP(3) receptor (IP(3)R) expression [2].
• We further hypothesize that the tonically elevated expression of chromogranin A, a reportedly master control "switch" for dense core granule formation, may contribute to the process driving glandular hypertrophy and chromaffin cell hyperplasia in the Anx7 (+/-) mutant mouse [2].
• Distinct Effects of Annexin A7 and p53 on Arachidonate Lipoxygenation in Prostate Cancer Cells Involve 5-Lipoxygenase Transcription [3].
• Here we have analyzed the distribution of annexin VII in muscle disorders in which the Ca2+ regulation is affected [4].

High impact information on Anxa7

• As hypothesized, the Anx7(+/-) mouse has a cancer-prone phenotype [5].
• Haploinsufficiency of Anx7 tumor suppressor gene and consequent genomic instability promotes tumorigenesis in the Anx7(+/-) mouse [5].
• Ca(2+)-induced and cyclic AMP-mediated potentiation of insulin secretion was unchanged in the absence of annexin A7, suggesting that it is not directly implicated in vesicle fusion [6].
• Annexin A7 has been proposed to function in the fusion of vesicles, acting as a Ca(2+) channel and as Ca(2+)-activated GTPase, thus inducing Ca(2+)/GTP-dependent secretory events [6].
• Alternative splicing of human synexin mRNA in brain, cardiac, and skeletal muscle alters the unique N-terminal domain [7].

Biological context of Anxa7

• Our results favor an involvement of annexin A7 in Ca(2+)-dependent signaling or Ca(2+) homeostasis in astrocytes [8].
• A search for annexin A7 binding partners with advanced biochemical methods confirmed sorcin as the major binding protein [8].
• Two sets of cDNAs encoding mouse synexin were isolated from a liver cDNA library and sequenced [9].
• The amino acid sequence of mouse synexin shows a high degree of similarity to both the unique N-terminal domain and the highly conserved C-terminal domain of previously cloned human synexin [9].
• We have isolated and characterized the gene encoding mouse synexin, which consists of 14 exons and spans approximately 30 kbp of genomic DNA [10].

Anatomical context of Anxa7

• The lack of annexin A7 affects functions of primary astrocytes [8].
• The results obtained indicate a developmentally and Ca(2+)-regulated localization and expression of annexin VII and raise the possibility that annexin VII may play a role in excitation-contraction coupling in skeletal muscle [1].
• In the presence of 100 microM extracellular Ca2+, annexin VII remained bound to the plasma membrane even in the presence of high digitonin concentrations [1].
• Immunofluorescence showed that annexin VII was located in the cytosol of mononucleated and fused polynucleated cultured cells, whereas in striated muscle, annexin VII was located preferentially at the plasma membrane and the transverse tubules [1].
• We used PCR to isolate from a lambda gt11-mouse fibroblast library annexin VII cDNA fragments corresponding to the two isoforms found in both humans and Dictyostelium discoideum [1].

Associations of Anxa7 with chemical compounds

• Annexin A7 is a Ca(2+)- and phospholipid-binding protein, which is thought to function in membrane organization and Ca(2+)-dependent signaling processes [8].
• Permeabilization of L6 cells with digitonin in the presence of 5 mM EGTA led to a release of annexin VII from the cells, which paralleled the loss of cytosolic lactate dehydrogenase (LDH) at low detergent concentrations (50 microM) [1].
• Incubation with the Ca(2+)-specific ionophore A23187 and 100 microM extracellular Ca2+ led to a redistribution of annexin VII from the cytosol to the plasma membrane after 30 minutes of incubation [1].
• We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/-) mouse remain low [11].
• Partial truncation of the NH2-terminus affects physical characteristics and membrane binding, aggregation, and fusion properties of annexin A7 [12].

Physical interactions of Anxa7

• In turn, the lack of complex formation between the sorcin Ca(2+) binding domain (33-198) and synexin maps the annexin binding site to the N-terminal region of the sorcin polypeptide chain [13].

Other interactions of Anxa7

• The interaction may involve similar structural motifs in the two proteins, namely GGYY and GYGG in sorcin and GYPP in synexin [13].
• Neuronal cells of all areas in the adult brain present Annexin A7 in the nucleus, whereas glial fibrillary acidic protein (GFAP)-positive astrocytes exhibit both, a cytoplasmic and nuclear staining [14].
• Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver [11].
• A remarkable difference was observed in muscle specimens from patients suffering from Duchenne muscular dystrophy and also in muscle from the MDX mouse where annexin VII was gradually released from the sarcolemmal membrane into the cytosol and into the extracellular space during progression of the disease [4].

Analytical, diagnostic and therapeutic context of Anxa7

• Both mouse liver synexin and recombinant mouse synexin expressed in Escherichia coli reacted after Western-blot analysis with a goat antibody against bovine synexin [9].
• RESULTS: Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state [11].
• Surface plasmon resonance experiments show that at neutral pH the stability of the complex between sorcin and annexin VII (synexin) increases dramatically between 3 and 6 microM calcium; at the latter cation concentration the K(D) value is 0.63 microM [13].
• By immunohistochemistry analysis Annexin A7 was detected in the cytosol of undifferentiated cells at embryonic days E5-E8 [14].
• In immunofluorescence and cell fractionation studies annexin VII was found in the cytoplasm and on the plasma membrane [15].

References