High impact information on cm

• A new adaptor protein complex, termed AP-3, has recently been identified in mammalian cells, and genetic studies in yeast have revealed a functional role for the AP-3 complex in cargo-selective transport via a new alternative trafficking pathway from the Golgi to the vacuole/lysosome [1].
• We are calling this complex AP-3, a name that has also been used for the neuronalspecific phosphoprotein AP180, but we feel that it is a more appropriate designation for an adaptor-related heterotetramer [2].
• Because pigment granules are believed to be similar to lysosomes, this suggests either that the AP-3 complex may be directly involved in trafficking to lysosomes or alternatively that it may be involved in another pathway, but that missorting in that pathway may indirectly lead to defects in pigment granules [2].
• One of the mutant chromosomes had an active hobo-mediated instability, manifested by the recurrent production of mutations of the carmine (cm) locus in bands 6E5-6 [3].
• Our findings implicate the Drosophila torsin, torp4a, to function with molecules consistent with already predicted roles in the endoplasmic reticulum/nuclear envelope compartment, and have identified potential new interactions with AP-3 like components [4].

Biological context of cm

• Together, these results demonstrate that Drosophila AP-3 is critical for the biogenesis of pigment granules, but is apparently not essential for formation of a major population of synaptic vesicles in vivo [5].
• DmP0 is a multifunctional protein necessary for efficient protein translation of the 60S ribosome as well as DNA repair via AP3 endonuclease activity [6].
• Our studies demonstrate that the lack of AP-3 does not affect the kinetics of invariant chain degradation, the route of class II-invariant chain transport, or the rate and extent of class II-peptide binding as assessed by the generation of SDS-stable dimers [7].

Anatomical context of cm

• The adaptor protein (AP) complexes AP-1, AP-2, and AP-3 mediate coated vesicle formation and sorting of integral membrane proteins in the endocytic and late exocytic pathways in mammalian cells [8].
• Recent molecular analysis indicates that it encodes the delta subunit of the AP-3 adaptin complex involved in vesicle transport from the trans-Golgi network to lysosomes and related organelles, such as pigment granules [9].
• Here we compare the relative importance of AP-3 in the biogenesis of these organelles in Drosophila melanogaster [5].
• The AP-3 adaptor protein complex has been implicated in the biogenesis of lysosome-related organelles, such as pigment granules/melanosomes, and synaptic vesicles [5].

Associations of cm with chemical compounds

• Medium chain and delta-COP genes were cytologically mapped and the mu3 gene was found to localize to a region containing the pigmentation locus carmine (cm) [8].
• Variation in relative 0.98 and 1.00 AP-3 allozyme activities of chromosome 3 isogenic strains was examined on acrylamide gels in F1 heterozygotes obtained by crossing these strains individually to a reference strain with a slower 0.87 mobility allozyme [10].

Other interactions of cm

• The additive effect on pigmentation and the predicted protein products of these genes suggest that the garnet/AP-3 transport system ensures the correct intracellular localization of the white gene product [9].

Analytical, diagnostic and therapeutic context of cm

• Immunofluorescence using anti-delta antibodies reveals that the AP-3 complex is associated with the Golgi region of the cell as well as with more peripheral structures [2].
• Electron microscopy reveals dramatic reductions in the numbers of electron-dense pigment granules in the eyes of these AP-3 mutants [5].

References