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The Journal of Neuroscience, August 6, 2008, 28(32):7954-7967; doi:10.1523/JNEUROSCI.1964-08.2008
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Cellular/Molecular
Multiple RIBEYE–RIBEYE Interactions Create a Dynamic Scaffold for the Formation of Synaptic Ribbons
Venkat Giri Magupalli,1 Karin Schwarz,1 Kannan Alpadi,1 Sivaraman Natarajan,1 Gail M. Seigel,2 andFrank Schmitz1 1Department of Neuroanatomy, Institute for Anatomy and Cell Biology, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany, and 2Department of Ophthalmology, Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214
Correspondence should be addressed to Dr. Frank Schmitz, Department of Neuroanatomy, Institute for Anatomy and Cell Biology, Saarland University, Medical School Homburg/Saar, Kirrbergerstrasse, Building 61, 66421 Homburg/Saar, Germany. Email: frank.schmitz{at}uniklinik-saarland.de
Synaptic ribbons are large, dynamic structures in the active zone complex of ribbon synapses and important for the physiological properties of these tonically active synapses. RIBEYE is a unique and major protein component of synaptic ribbons. The aim of the present study was to understand how the synaptic ribbon is built and how the construction of the ribbon could contribute to its ultrastructural plasticity. In the present study, we demonstrate that RIBEYE self-associates using different independent approaches (yeast two-hybrid analyses, protein pull downs, synaptic ribbon–RIBEYE interaction assays, coaggregation experiments, transmission electron microscopy and immunogold electron microscopy). The A-domain [RIBEYE(A)] and B-domain [RIBEYE(B)] of RIBEYE contain five distinct sites for RIBEYE–RIBEYE interactions. Three interaction sites are present in the A-domain of RIBEYE and mediate RIBEYE(A)–RIBEYE(A) homodimerization and heterodimerization with the B-domain. The docking site for RIBEYE(A) on RIBEYE(B) is topographically and functionally different from the RIBEYE(B) homodimerization interface and is negatively regulated by nicotinamide adenine dinucleotide. The identified multiple RIBEYE–RIBEYE interactions have the potential to build the synaptic ribbon: heterologously expressed RIBEYE forms large electron-dense aggregates that are in part physically associated with surrounding vesicles and membrane compartments. These structures resemble spherical synaptic ribbons. These ribbon-like structures coassemble with the active zone protein bassoon, an interaction partner of RIBEYE at the active zone of ribbon synapses, emphasizing the physiological relevance of these RIBEYE-containing aggregates. Based on the identified multiple RIBEYE–RIBEYE interactions, we provide a molecular mechanism for the dynamic assembly of synaptic ribbons from individual RIBEYE subunits.
Key words: synaptic ribbon; ribbon synapse; RIBEYE; retina; active zones; exocytosis
Received Jan. 29, 2008; revised June 21, 2008; accepted June 21, 2008.
Correspondence should be addressed to Dr. Frank Schmitz, Department of Neuroanatomy, Institute for Anatomy and Cell Biology, Saarland University, Medical School Homburg/Saar, Kirrbergerstrasse, Building 61, 66421 Homburg/Saar, Germany. Email: frank.schmitz{at}uniklinik-saarland.de
This article has been cited by other articles:
L. LoGiudice and G. Matthews
The Role of Ribbons at Sensory Synapses
Neuroscientist, August 1, 2009; 15(4): 380 - 391.
[Abstract] [PDF]
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