| First Author | Szodorai A | Year | 2009 |
| Journal | J Neurosci | Volume | 29 |
| Issue | 46 | Pages | 14534-44 |
| PubMed ID | 19923287 | Mgi Jnum | J:155752 |
| Mgi Id | MGI:4415645 | Doi | 10.1523/JNEUROSCI.1546-09.2009 |
| Citation | Szodorai A, et al. (2009) APP anterograde transport requires Rab3A GTPase activity for assembly of the transport vesicle. J Neurosci 29(46):14534-44 |
| abstractText | The amyloid precursor protein (APP) is anterogradely transported by conventional kinesin in a distinct transport vesicle, but both the biochemical composition of such a vesicle and the specific kinesin-1 motor responsible for transport are poorly defined. APP may be sequentially cleaved by beta- and gamma-secretases leading to accumulation of beta-amyloid (Abeta) peptides in brains of Alzheimer's disease patients, whereas cleavage of APP by alpha-secretases prevents Abeta generation. Here, we demonstrate by time-lapse analysis and immunoisolations that APP is a cargo of a vesicle containing the kinesin heavy chain isoform kinesin-1C, the small GTPase Rab3A, and a specific subset of presynaptic protein components. Moreover, we report that assembly of kinesin-1C and APP in this vesicle type requires Rab3A GTPase activity. Finally, we show cleavage of APP in transport vesicles by alpha-secretase activity, likely mediated by ADAM10. Together, these data indicate that maturation of APP transport vesicles, including recruitment of conventional kinesin, requires Rab3 GTPase activity. |
