Speaker: Victor Faundez, M.D., Ph.D.

Associate Professor
Department of Cell Biology
Emory University
Atlanta, GA

website :http://cellbio.emory.edu/faculty_detail.cfm?id=1392
  

Topic:

" Mechanisms of Endosome Traffic in Neurons"

A defining feature of presynaptic terminals is the presence of synaptic vesicles (SVs), secretory organelles that store and secrete neurotransmitters. SVs functions are specified by the organelle membrane protein composition. Thus, mechanisms controlling SV formation and composition are pivotal for synapse function. During my presentation I will focus on the vesicle biogenesis pathway controlled by the adaptor complex AP-3, a coat complex that sorts membrane proteins from early endosomes to SVs. SV protein composition is regulated by two isoforms of the adaptor complex AP-3, neuronal and ubiquitous, the later thought to participate exclusively in lysosome biogenesis. Genetic defects in the neuronal AP-3 isoform hinder targeting of SV membrane proteins. Surprisingly, null mouse mutants in a lysosomal sorting pathway, the ubiquitous AP-3 route, trigger accruement of SV-specific proteins in SVs. These unexpected results lead us to propose the novel concept that SV and lysosomal sorting mechanisms present on the same endosome compete for membrane proteins to be delivered into two alternative routes, SVs or lysosomes. This concept departs from the traditional view of lysosomes, which are viewed as terminal organelles involved in the disposal of normal and pathological cellular components.

When:

Monday, April 16, 2007
12:00PM – 1:00PM
 

Location:

Baldwin Auditorium
Robert H. Lurie Medical Research Center
303 East Superior Street, 1st floor
  

Hosted by Dr. Kathy Green, Ph.D

Newell-Litwa K, Seong E, Burmeister M, Faundez V.Neuronal and non-neuronal functions of the AP-3 sorting machinery. J Cell Sci. 2007 Feb 15;120(Pt 4):531-41.

Styers ML, Kowalczyk AP, Faundez V. Architecture of the vimentin cytoskeleton is modified by perturbation of the GTPase ARF1. J Cell Sci. 2006 Sep 1;119(Pt 17):3643-54. Epub 2006 Aug 15.

Werner E, Kowalczyk AP, Faundez V. Anthrax toxin receptor 1/tumor endothelium marker 8 mediates cell spreading by coupling extracellular ligands to the actin cytoskeleton. J Biol Chem. 2006 Aug 11;281(32):23227-36. Epub 2006 Jun 8.

Procaccio V, Salazar G, Ono S, Styers ML, Gearing M, Davila A, Jimenez R, Juncos J, Gutekunst CA, Meroni G, Fontanella B, Sontag E, Sontag JM, Faundez V, Wainer BH.A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia.
Am J Hum Genet. 2006 Jun;78(6):947-60. Epub 2006 Apr 21.

Berger AC, Vanderford TH, Gernert KM, Nichols JW, Faundez V, Corbett AH. Saccharomyces cerevisiae Npc2p is a functionally conserved homologue of the human Niemann-Pick disease type C 2 protein, hNPC2.
Eukaryot Cell. 2005 Nov;4(11):1851-62.