APP anterograde transport requires Rab3A GTPase activity for assembly of the transport vesicle.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Anita SzodoraiStefan Kins

Abstract

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.

References

Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·E H KooD L Price
Mar 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·G Fischer von MollardT C Südhof
Sep 1, 1984·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J P Kratohvil
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·Z W LiC Weissmann
Dec 10, 1999·Molecular Biology of the Cell·H de WitJ Klumperman
Mar 7, 2001·Cellular and Molecular Life Sciences : CMLS·T DresbachE D Gundelfinger
Nov 12, 2002·The EMBO Journal·Toshiaki SakisakaWilliam E Balch
May 17, 2003·Critical Reviews in Biochemistry and Molecular Biology·Magdalena DenekaPeter van der Sluijs
Jul 23, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Oliver M SchlüterThomas C Südhof
Oct 14, 2004·The Journal of Cell Biology·Carolyn J LawrenceLinda Wordeman
Feb 4, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Pei WangHui Zheng
Mar 5, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Orly LazarovSangram S Sisodia
Jul 27, 2005·Biochemical Society Transactions·B R Ali, M C Seabra
Sep 6, 2005·The Journal of Physiology·Erin N StarVenkatesh N Murthy
Sep 30, 2005·The EMBO Journal·Peter SobaKonrad Beyreuther
Oct 28, 2005·The EMBO Journal·Constanze ReinhardBart De Strooper
Jan 27, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Oliver M SchlüterChristian Rosenmund
May 11, 2006·Journal of Cell Science·Takashi Tsuboi, Mitsunori Fukuda
Jun 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ayuko SakaneTakuya Sasaki
Oct 20, 2006·The Journal of Biological Chemistry·Yung-Hui KuanStefan Kins
Oct 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Prasanna Satpute-KrishnanElaine L Bearer
Nov 18, 2006·Cell·Shigeo TakamoriReinhard Jahn
Feb 22, 2007·Journal of Cell Science·Mark T W HandleyRobert D Burgoyne
Jun 29, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Orly LazarovSangram S Sisodia
Mar 26, 2008·Biochemistry·Scott R DeBoerGerardo Morfini

❮ Previous
Next ❯

Citations

Sep 21, 2011·Experimental Brain Research·Dorothee AydinUlrike C Müller
Oct 1, 2011·Experimental Brain Research·Silke BrunholzGerardo Morfini
Feb 23, 2012·Experimental Brain Research·W Volknandt, M Karas
Mar 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·John Jia En ChuaReinhard Jahn
May 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Lukasz SzpankowskiLawrence S B Goldstein
Mar 9, 2012·Molecular Biology of the Cell·Gerald F ReisLawrence S B Goldstein
Mar 22, 2012·Human Molecular Genetics·Alessio VagnoniChristopher C J Miller
Jul 31, 2012·Human Molecular Genetics·Elizabeth M RodriguesLawrence S B Goldstein
May 4, 2012·Cold Spring Harbor Perspectives in Medicine·Christian HaassSangram Sisodia
Feb 23, 2012·Cold Spring Harbor Perspectives in Medicine·Ulrike C Müller, Hui Zheng
May 11, 2011·PloS One·Teja W GroemerJürgen Klingauf
Apr 16, 2013·PloS One·Xiaomin ZhangAndreas Draguhn
Sep 18, 2013·Journal of Neuropathology and Experimental Neurology·Kenneth HensleyMarni E Harris-White
May 26, 2012·Cellular Signalling·Sylvie ClaeysenPatrizia Giannoni
May 15, 2010·Current Opinion in Cell Biology·Anna Akhmanova, John A Hammer
Aug 24, 2010·The European Journal of Neuroscience·Laura K HamiltonKarl J L Fernandes
Jul 3, 2013·Journal of Neurochemistry·Melanie LaßekWalter Volknandt
Aug 10, 2011·Journal of Neurochemistry·Jaehong SuhSuzanne Y Guénette
Feb 13, 2014·Journal of Neurochemistry·David Villarroel-CamposChristian Gonzalez-Billault
Apr 17, 2015·BMC Neuroscience·Aysegul Dilsizoglu SenolBernadette Allinquant
Dec 20, 2014·Molecular Neurodegeneration·Catherine MarquerMarie-Claude Potier
Dec 4, 2012·Mechanisms of Development·John H CaldwellUlrike C Müller
Jul 21, 2014·Cell and Tissue Research·Melanie LaßekWalter Volknandt
Oct 26, 2016·Brain Research Bulletin·Gerardo MorfiniStefan Kins
Feb 2, 2017·Small GTPases·Maria Lidia Mignogna, Patrizia D'Adamo
Feb 9, 2017·Journal of Neuropathology and Experimental Neurology·Viktoria GudiThomas Skripuletz
Oct 25, 2017·Journal of Alzheimer's Disease : JAD·Kelly HaresAlastair Wilkins
Dec 16, 2017·Nature Reviews. Neurology·Juan Carlos PolancoJürgen Götz
May 5, 2018·Journal of Cell Science·María Gabriela OteroTomás Luis Falzone
Feb 12, 2019·Critical Reviews in Biochemistry and Molecular Biology·S ParakhJ D Atkin
Mar 7, 2018·Proceedings. Mathematical, Physical, and Engineering Sciences·I A Kuznetsov, A V Kuznetsov

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Endosomes

Dysfunctional endosomal trafficking may be associated with Alzheimer’s disease (AD) pathology. Targeting the endosome may advance treatment options for AD. Here is the latest research on endosomes and AD.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.