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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-26530

Szodorai, A; Kuan, Y H; Hunzelmann, S; Engel, U; Sakane, A; Sasaki, T; Takai, Y; Kirsch, J; Müller, U; Beyreuther, K; Brady, S; Morfini, G; Kins, S (2009). APP anterograde transport requires Rab3A GTPase activity for assembly of the transport vesicle. Journal of Neuroscience, 29(46):14534-14544.



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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
DDC:610 Medicine & health
Deposited On:13 Jan 2010 09:48
Last Modified:27 Nov 2013 23:18
Publisher:Society for Neuroscience
Additional Information:Holder of copyright: The Society for Neuroscience
Publisher DOI:10.1523/JNEUROSCI.1546-09.2009
PubMed ID:19923287
Citations:Web of Science®. Times Cited: 37
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Scopus®. Citation Count: 36

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