| First Author | Larimore J | Year | 2011 |
| Journal | Mol Biol Cell | Volume | 22 |
| Issue | 24 | Pages | 4854-67 |
| PubMed ID | 21998198 | Mgi Jnum | J:187545 |
| Mgi Id | MGI:5437407 | Doi | 10.1091/mbc.E11-07-0592 |
| Citation | Larimore J, et al. (2011) The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse. Mol Biol Cell 22(24):4854-67 |
| abstractText | Dysbindin assembles into the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which interacts with the adaptor protein complex 3 (AP-3), mediating a common endosome-trafficking route. Deficiencies in AP-3 and BLOC-1 affect synaptic vesicle composition. However, whether AP-3-BLOC-1-dependent sorting events that control synapse membrane protein content take place in cell bodies upstream of nerve terminals remains unknown. We tested this hypothesis by analyzing the targeting of phosphatidylinositol-4-kinase type II alpha (PI4KIIalpha), a membrane protein present in presynaptic and postsynaptic compartments. PI4KIIalpha copurified with BLOC-1 and AP-3 in neuronal cells. These interactions translated into a decreased PI4KIIalpha content in the dentate gyrus of dysbindin-null BLOC-1 deficiency and AP-3-null mice. Reduction of PI4KIIalpha in the dentate reflects a failure to traffic from the cell body. PI4KIIalpha was targeted to processes in wild-type primary cultured cortical neurons and PC12 cells but failed to reach neurites in cells lacking either AP-3 or BLOC-1. Similarly, disruption of an AP-3-sorting motif in PI4KIIalpha impaired its sorting into processes of PC12 and primary cultured cortical neuronal cells. Our findings indicate a novel vesicle transport mechanism requiring BLOC-1 and AP-3 complexes for cargo sorting from neuronal cell bodies to neurites and nerve terminals. |
