Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular processes rely on dynamic events occurring between the cortical cytoskeleton and plasma membrane. Members of the Band 4.1 superfamily, which are best known for their ability to tether the cytoskeleton to the plasma membrane, play prominent structural and regulatory roles that influence cell-cell and cell-substrate interactions, endo- and exocytosis, cell polarity, migration, proliferation, and differentiation. We have identified a new member of the zebrafish Band 4.1 superfamily, which is the homolog of human myosin regulatory light chain interacting protein (MIR), and have examined its role in embryonic development. Zebrafish Mir contains the conserved amino-terminal plasma membrane-binding FERM (Band 4.1/ezrin/radixin/moesin) domain as well as other putative protein-protein interacting domains, including a RING finger. Overall, zebrafish Mir is 71% identical to human MIR located at chromosome 6p23-p22.3, and maps on linkage group 19 to a region of synteny with human chromosome 6. In situ hybridization and RT-PCR revealed that mir is expressed maternally and ubiquitously throughout development. Blocking Mir translation using a mir-specific, morpholino-based, knock-down strategy or expressing Mir constructs lacking the RING finger domain disrupts gastrulation and leads to subsequent trunk and tail defects. In severe cases, morphants exogastrulate. The synergistic effect seen when two mir-specific morpholinos are used in conjunction reflects the specific knock-down of mir. In addition, morphant phenotypes induced by mir-specific morpholinos are rescued by overexpression of the full-length Mir. In situ hybridization analysis with mesodermal- and neural-specific markers shows that morphants exhibit a delay in cell movements associated with gastrulation, epiboly, convergence, and extension. A yeast two-hybrid analysis was performed to identify binding partners that may participate with Mir during gastrulation, and Annexin V, a calcium channel protein, was isolated. At early developmental stages, annexin V transcripts colocalize with mir, but after gastrulation, annexin V mRNA becomes localized to the distal tail region and an area in the olfactory placode. At the protein level, Mir colocalizes with Annexin V when expressed in COS cells. Together, these results indicate that Mir is essential for embryonic development and that its role in early embryonic development likely involves calcium-dependent mechanisms essential during the extensive cell movements associated with gastrulation.
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PMID:The zebrafish band 4.1 member Mir is involved in cell movements associated with gastrulation. 1465 27

Although Xenopus studies have shown that Frizzled 7 activates at least two noncanonical signaling pathways, it is less clear which, if any, of these signaling pathways are downstream of Frizzled 7 in zebrafish. Cotransfection of Frizzled 7a (Fz7a) or Frizzled 7 (Fz7) and Xenopus Dsh-GFP results in the translocation of Dsh from the cytoplasm to the plasma membrane, a key step in canonical and noncanonical Wnt signaling. Overexpression of both zebrafish Frizzled 7 orthologs perturbs gastrulation, leading to tail defects. Rescue experiments using downstream components of the Xenopus noncanonical Wnt pathways indicate that zebrafish Fz7a and Fz7 signal through different noncanonical components. Although co-injection of pertussis toxin or a dominant negative Cdc42 rescues incomplete gastrulation caused by Fz7a, neither has any significant effect on Fz7 induced gastrulation defects. Likewise, the Fz7 overexpression phenotype, but not that of Fz7a, is rescued by myosin regulatory light chain interacting protein (Mir) and its binding partner Annexin V. Together these results indicate that Fz7a and Fz7 signal through different pathways during zebrafish gastrulation, and that Mir and Annexin V antagonize Fz7 signaling.
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PMID:Zebrafish Mir antagonizes Frizzled 7-induced gastrulation defects. 1824 25