Mechanismen der Endocytose von synaptischen Vesikeln
Final Report Abstract
Synaptic transmission is a complex progression of sequential steps many proteins are involved in. All steps starting with the fusion of a vesicle, ending with the recycling of the membrane and the formation of a new vesicle are precisely regulated to ensure an constant ongoing signal transmission between two neurons. Many proteins are involved to ensure that a vesicle fuses at a certain position at the right time, that a single vesicle with the right set of proteins is recycled and rejoins the vesicle pool. Over the last decade scientists have identified and characterized many proteins regulating different steps along this way. However not all proteins are known yet and there still remain open questions. How is vesicle fusion and vesicle recycling temporally coupled, what is the actual signal inducing vesicle endocytosis, are the vesicle proteins randomly picked up or do they stay as a cluster together, how is the final scission process regulated, is dynamin the only protein performing fission or is it a complex of many proteins? With this project we are able to answer some of these questions. Using SUPER templates we can show that dynamin is able to perform fission on its own. In contrast EHD which does have a comparable structure hydrolysing ATP instead of GTP is not able to induce scission on SUPER templates. However it is able to negatively influencing dynamin fission. It regulates the length of the progressing neck of the coated pit and ensures that the scission process is efficient. So far a function for EHD has only been described in endocytic membrane trafficking processes in non neuronal cells. Our results are the first indications that EHD is also present in neuronal cells and does have a role in vesicle endocytosis. It is a new component of the complex protein network regulating vesicle endocytosis. So far only proteins promoting dynamin function were described like endophilin EHD is the first protein actually having a negative impact on dynamin. With this study we are able to make a contribution to a better understanding of the molecular mechanisms leading to precise vesicle recycling.
Publications
- Syndapin and synaptic endocytosis. In: Dowler, B.C. (Ed) Endocytosis: Structural Components, Functions and Pathways, Nova Science Publishers, NY, 2010 pp. 191-201
Lennart Brodin, Joel Jakobsson, Frauke Ackermann, Fredrik Andersson, Peter Löw
- The “acrosomal synapse”: Subcellular organization by lipid rafts and scaffolding proteins exhibits high similarities in neurons and mammalian spermatozoa. Commun Integr Biol. 2010 Nov; 3(6):513-21
Nele Zitranski, Heike Borth, Frauke Ackermann, Dorke Meyer, Laura Viewig, Andreas Breit, Thomas Gudermann, Ingrid Boekhoff
- Regulation of Synaptic Vesicle Budding and Dynamin Function by an EHD ATPase. J. Neurosci. 2011 Sep 28;31 (39): 13972-80
Joel Jakobsson, Frauke Ackermann, Fredrik Andersson, Dan Larhammer, Peter Löw, Lennart Brodin
- Soluble membrane trafficking proteins taking a break at silent synaptic vesicles. Proc Natl Acad Sci USA. 2011 Oct 11; 108 (41):16869-70
Lennart Brodin, Joshua Gregory, Frauke Ackermann
