Disease relevance of Fas3

• In insects, fasciclin II is present on a restricted subset of embryonic central nervous system axons where it controls selective axon fasciculation [1].
• Secreted fasciclin III is expressed at 35 to 40 mg/l in insect cells with baculovirus carrying the recombinant gene [2].

High impact information on Fas3

• Sequence analysis reveals that fasciclin III encodes a transmembrane protein with no significant homology to any known protein, including the previously characterized families of vertebrate cell adhesion molecules [3].
• The distribution of this adhesion molecule on subsets of fasciculating axons and growth cones during Drosophila development suggests that fasciclin III plays a role in growth cone guidance [3].
• Drosophila fasciclin III is an integral membrane glycoprotein that is expressed on a subset of neurons and fasciculating axons in the developing CNS, as well as in several other tissues during development [3].
• We report here that RP3 often incorrectly innervates neighbouring non-target muscle cells when these cells misexpress fasciclin III, but still innervates normal targets in the fasciclin III null mutant [4].
• Fasciclin III manipulations do not influence target selections by other motor neurons, including fasciclin III-expressing RP1 [4].

Biological context of Fas3

• Among 900 lines with expression of the boss reporter gene in multiple cells assessed for homozygous mutant phenotypes, insertions in the marbles, glass, gap1, and fasciclin II genes were isolated [5].
• Fasciclin II controls proneural gene expression in Drosophila [6].
• In this paper we examine in detail the expression of fasciclin I mRNA and protein during Drosophila embryonic development [7].
• Furthermore, in slmb somatic clones, we observed ectopic Fasciclin 3 expression, suggesting a delay in follicle cell differentiation, which correlated with the occurrence of ectopic polar cells, lack of interfollicular stalks and mislocalization of the oocyte [8].
• This model is a de novo test of the sequence-to-structure alignment algorithm and is currently being used as the basis for mutagenesis experiments to discern the parts of the fasciclin III protein that are necessary for homophilic molecular recognition in the developing Drosophila nervous system [9].

Anatomical context of Fas3

• When Fasciclin III (Fas3), a "positive" target recognition molecule for RP3, is ectopically expressed in neighboring muscles, the RP3 growth cone ectopically develops membrane contact sites with Fas3-misexpressing muscles with which it would not normally associate [10].
• Fasciclin III, a cell adhesion molecule of the immunoglobulin superfamily, is expressed by motor neuron RP3 and its synaptic targets (muscle cells 6 and 7) during embryonic neuromuscular development of Drosophila [4].
• We propose that fasciclin III acts as a synaptic target recognition molecule for motor neuron RP3, and also that its absence can be compensated for by other molecule(s) [4].
• Within presynaptic terminals, HIW is localized to the periactive zone surrounding active zones; Fasciclin II (Fas II), which also controls synaptic growth, is found at the same location [11].
• In wit mutant larvae, the size of the NMJs is greatly reduced relative to the size of the muscles. wit NMJs have reduced evoked excitatory junctional potentials, decreased levels of the synaptic cell adhesion molecule Fasciclin II, and synaptic membrane detachment at active zones [12].

Associations of Fas3 with chemical compounds

• The existence of an initial phase of expression on all commissural bundles helps to explain the loss-of-commissures phenotype of embryos lacking expression of both fasciclin I and of the D-abl tyrosine kinase [7].
• Single crystals of purified soluble fasciclin III have been grown by vapor diffusion versus polyethylene glycol 8000/sodium citrate at low pH [2].

Regulatory relationships of Fas3

• Consistent with this hypothesis, the Broad and rho-lacZ cells express different levels of the homophilic adhesion molecule Fasciclin 3 [13].

Other interactions of Fas3

• Furthermore, Nkx6 is necessary for the expression of the neural adhesion molecule Fasciclin III in Nkx6-positive motoneurons [14].
• Drosophila fasciclin I is a novel homophilic adhesion molecule that along with fasciclin III can mediate cell sorting [15].
• 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 [16].
• Previous studies have shown that both the Fasciclin II (Fas II) cell adhesion molecule and the Shaker potassium channel are localized at the Drosophila neuromuscular junction, where they function in the growth and plasticity of the synapse [17].

Analytical, diagnostic and therapeutic context of Fas3

• Antisera generated against each of four highly related forms of the protein were used for cDNA expression cloning to identify a single gene, which was confirmed to encode fasciclin III by tissue in situ hybridization and genetic deficiency analysis [18].
• A truncated form of Drosophila fasciclin III has been engineered by site-directed mutagenesis [2].
• Expression and crystallization of a soluble form of Drosophila fasciclin III [2].

References