Molecular mechanisms controlling organization of endocytic zones in synapses
Zusammenfassung der Projektergebnisse
In the pesent study we could show that intersectin has a dynamic localization in the lamprey giant synapse depending on stimulation. After stimulation it relocates from the synaptic vesicle cluster to endocytic sites. During this cycle intersectin negatively controls the relocalization of dynamin, its major binding partner, from the vesicle cluster to the periactive zone. In addition, intersectin seems to facilitate the function of dynamin during fission of synaptic vesicles. Since the migration of dynamin and intersectin to the periactive zone is also efficiently performed when the intersectin-dynamin interaction is perturbed, the two proteins must be targeted via independent mechanisms. It has been shown that the targeting of intersectin to the coat occurs via its Eps15 interaction. For dynamin several SH3 domain proteins have been proposed to perform this role (e.g. intersectin, amphiphysin, synadapin, and cortactin). It remains to be clarified which of these proteins delivers dynamin to the endocytic zone. Our study shows that the intersectin-dynamin interactions are important during fission of synaptic vesicles. In the case of the antibody injections more dynamin was found on clathrin coated intermediates but the fission reaction was not efficient. This could mean that an active, defined positioning of dynamin is required for efficient membrane severing. Intersectin seems to function as an important regulatory protein in this process.
Projektbezogene Publikationen (Auswahl)
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"Intersectin is a negative regulator of Dynamin Recruitment to the Synaptic Endocytic Zone in the Central Synapse". The journal of neuroscience, 2007
E. Evergren, H. Gad, K. Walther et al.
