Synaptic vesicle alterations in rod photoreceptors of synaptophysin-deficient mice

• Published in: Neuroscience 2001-01, Vol.107 (1), p.127-142
• Main Authors: Spiwoks-Becker, I, Vollrath, L, Seeliger, M.W, Jaissle, G, Eshkind, L.G, Leube, R.E
• Format: Article
• Language: English
• Subjects: Action Potentials - genetics; Animals; Biological and medical sciences; Clathrin-Coated Vesicles - pathology; Clathrin-Coated Vesicles - ultrastructure; Dark Adaptation - genetics; Electroretinography; ERG; Exocytosis - genetics; Eye and associated structures. Visual pathways and centers. Vision; Female; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; knockout mouse; Male; Membrane Proteins - deficiency; Membrane Proteins - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron; Photic Stimulation; Presynaptic Terminals - pathology; Presynaptic Terminals - ultrastructure; Protein Transport - genetics; retina; Retinal Rod Photoreceptor Cells - abnormalities; Retinal Rod Photoreceptor Cells - pathology; Retinal Rod Photoreceptor Cells - ultrastructure; ribbon synapse; Sex Characteristics; Synaptic Transmission - genetics; synaptic vesicle protein; Synaptic Vesicles - metabolism; Synaptic Vesicles - pathology; Synaptic Vesicles - ultrastructure; Synaptophysin - deficiency; Synaptophysin - genetics; Vertebrates: nervous system and sense organs; vesicle traffic
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(01)00345-1

The abundance of the integral membrane protein synaptophysin in synaptic vesicles and its multiple possible functional contributions to transmitter exocytosis and synaptic vesicle formation stand in sharp contrast to the observed lack of defects in synaptophysin knockout mice. Assuming that deficiencies are compensated by the often coexpressed synaptophysin isoform synaptoporin, we now show that retinal rod photoreceptors, which do not synthesize synaptoporin either in wild-type or in knockout mice, are affected by the loss of synaptophysin. Multiple pale-appearing photoreceptors, as seen by electron microscopy, possess reduced cytoplasmic electron density, swollen mitochondria, an enlarged cell surface area, and, most importantly, a significantly reduced number of synaptic vesicles with an unusually bright interior. Quantification of the number of synaptic vesicles per unit area, not only in these, but also in all other rod terminals of knockout animals, reveals a considerable reduction in vesicles that is even more pronounced during the dark period, i.e., at times of highest synaptic activity. Moreover, activity-dependent reduction in synaptic vesicle diameter, typically occurring in wild-type mice, is not detected in knockout animals. The large number of clathrin-coated pits and vesicles in dark-adapted synaptophysin knockout mice is taken as an indication of compensatory usage of synaptophysin-independent pathway(s), and, conversely, in view of the overall reduction in the number of synaptic vesicles, as an indication for the presence of another synaptophysin-dependent synaptic vesicle recycling pathway. Our results provide in vivo evidence for the importance of the integral membrane protein synaptophysin for synaptic vesicle recycling and formation.