Disease relevance of Ank

• Parasitic arthropod Wolbachia are characterized by the presence of phages that carry ankyrin-repeat proteins; these proteins might be exported to the host cell to manipulate reproduction [1].

High impact information on Ank

• The molecular domains that are conserved in all members of the TRP family constitute parts of the transmembrane domains and in most members also the ankyrin-like repeats at the NH2 terminal of the protein and a "TRP domain" at the COOH terminal, which is a highly conserved 25-amino acid stretch with still unknown function [2].
• Finally, the phenotypes observed suggest that the cdc 10/ankyrin repeat region within the intracellular domain plays an essential role in the postulated signal transduction events [3].
• The trpl protein contains two possible calmodulin-binding sites, six transmembrane regions, and a sequence homologous to an ankyrin-like repeat [4].
• We use transgenic double-stranded RNA to selectively eliminate alpha-Spectrin, beta-Spectrin, or Ankyrin [5].
• Although Ankyrin is not required for the localization of the Spectrin skeleton to the neuromuscular junction, it contributes to Spectrin-mediated synapse development [5].

Biological context of Ank

• We provide evidence that neuroglian, a cell adhesion molecule related to L1 and neurofascin, can transmit positional information directly to ankyrin and thereby polarize its distribution in Drosophila S2 tissue culture cells [6].
• Expression of the L1 family cell adhesion molecule neuroglian in Drosophila S2 cells leads to cell aggregation and polarized ankyrin accumulation at sites of cell-cell contact [7].
• Whereas the previously described ankyrin gene is ubiquitously expressed during embryogenesis, the expression of Dank2 is restricted to the nervous system in the Drosophila embryo [8].
• Thus, the neuron-glia interaction that is mediated by Nrg, together with Ank under some situations, contributes to axonal and dendritic morphogenesis [9].
• However, residual recruitment of ankyrin by this mutant neuroglian molecule was still limited to cell contacts, indicating that the lack of ankyrin binding at noncontact sites is not caused by tyrosine phosphorylation [10].

Anatomical context of Ank

• Ankyrin was not normally associated with the plasma membrane of these cells [6].
• Thus neuroglian adhesion generates a spatial cue for polarized assembly of ankyrin and the spectrin cytoskeleton [7].
• Control of axonal sprouting and dendrite branching by the Nrg-Ank complex at the neuron-glia interface [9].
• In the Drosophila ovary, membrane skeletal proteins such as the adducin-like Hts protein(s), spectrin, and ankyrin are found in the spectrosome, an organelle in germline stem cells (GSC) and their differentiated daughter cells (cystoblasts) [11].
• We report here that certain embryonic cells and tissues that develop after lateral inhibition, like the connectives and commissures of the central nervous system, are enriched for a form of Notch not recognized by antibodies made against the intracellular region carboxy-terminal of the CDC10/Ankyrin repeats [12].

Associations of Ank with chemical compounds

• Mutation of a conserved tyrosine residue within this region reduced ankyrin binding and extracellular adhesion [10].
• We hypothesized that a tyrosine residue in the cytoplasmic domain of beta 1 may be important for ankyrin recruitment and tested our hypothesis using beta 1 mutants replacing Tyr(181) with alanine (beta 1Y181A), phenylalanine (beta 1Y181F), or glutamate (beta 1Y181E), or a truncated construct deleting all residues beyond Tyr(181) (beta 1L182(STOP)) [13].
• To determine the limits of cooperativity in a structurally modular protein, we characterized the structure and stability of glycine variants of the ankyrin repeat domain from the Drosophila melangaster Notch receptor [14].
• Fluorescence spectroscopy indicates that the single tryptophan in the fifth ankyrin repeat is in a nonpolar environment and is shielded from solvent in all three constructs, although slight differences in spectroscopic properties of the six- and five-repeat constructs are observed, indicating minor structural changes [15].
• We demonstrate that LPS induces a rapid processing event within the RELISH protein releasing the C-terminal ankyrin-repeats from the N-terminal Rel homology domain (RHD) [16].

Physical interactions of Ank

• The Drosophila L1-type protein neuroglian interacts with products from both Drosophila ankyrin genes [8].

Co-localisations of Ank

• This work identifies a tissue polarity gene, diego, that comprises six ankyrin repeats and colocalizes with Flamingo at proximal/distal boundaries [17].

Regulatory relationships of Ank

• Thus, neuroglian appears to be activated by extracellular adhesion so that ankyrin and the membrane skeleton selectively associate with sites of cell contact and not with other regions of the plasma membrane [6].

Other interactions of Ank

• Upon expression of an inducible neuroglian minigene, however, cells aggregated into large clusters and ankyrin became concentrated at sites of cell-cell contact [6].
• However, DE-cadherin expression had no detectable effect on the quantity or subcellular distribution of ankyrin or spectrin [18].
• In polarized cells, such as neurons, ankyrin-type proteins are the major molecules that link the actin-spectrin-based membrane cytoskeleton to the plasma membrane [19].
• In Drosophila the second ankyrin gene, Dank2, is exclusively expressed in neuronal cells [19].
• First, ankyrin and alphabeta-spectrin are not detected on the entire lateral surface but appear to be restricted to the apicolateral area, codistributing with fasciclin III at smooth septate junctions [20].

Analytical, diagnostic and therapeutic context of Ank

• Gel filtration chromatography and sedimentation equilibrium studies indicate that these ankyrin repeat polypeptides are monomeric [15].
• Circular dichroism (CD) spectroscopy indicates that Notch ankyrin polypeptides of different length contain a significant amount of alpha-helix, indicating that a folded structure can be maintained despite the loss of individual ankyrin modules [15].
• Molecular cloning and characterization of SRAM, a novel insect rel/ankyrin-family protein present in nuclei [21].

References