[5] Bacterial recombination also demonstrated heterotrimeric subcomplexes containing pallidin, cappucinno, and BLOS1 as well as dysbindin, Snapin, and BLOS-2 as important intermediate structures.
[5] Within the endomembrane system, BLOC-1 acts at the early endosome, as witnessed in electron microscopy experiments, where it helps coordinate protein-sorting of LAMPS (lysosome-associate membrane proteins).
[6] Multiple studies recapitulate an association with the adaptor complex AP-3, a protein involved in vesicular trafficking of cargo from the early endosome to lysosomal compartments.
[8] These studies demonstrate that BLOC-1 facilitates protein transport to lysosomal compartments, such as melanosomes, via multiple routes, although the exact functional association with BLOC-2 is unclear.
Still, it is clear BLOC-1 has an evolutionarily conserved importance in trafficking because its yeast homolog, which contains Vab2, has been proposed to modulate Rab5 (Vps21), which is essential for its membrane localization, by acting as a receptor on early endosomes for Rab5-GAP Msb3.
[3] Furthermore, proper neurite extension appears to be regulated by BLOC-1, which may have molecular links to the ability of BLOC-1 to physically associate in vitro with SNARE proteins such as SNAP-25, SNAP-17, and syntaxin 13.
[3] Studies in Drosophila melanogaster indicate pallidin is non-essential for synaptic vesicle homeostasis or anatomy but is essential under conditions of increased neuronal signaling to maintain vesicular trafficking from endosomes via recycling mechanisms.
[2] The effects of a non-functional Bloc1s6 gene (encoding for pallidin) on the metabolome of the post-natal mouse hippocampus were explored using LC-MS, revealing altered levels of a variety of metabolites.
[4] Overall, modifications in the metabolome of these mice extend to nucleobase molecules and lysophospholipids as well, implicating further dysregulation effects of BLOC-1 deficiencies to plausible molecular contributions of schizophrenia.