Synaptic vesicle alterations in rod photoreceptors of synaptophysin-deficient mice

The abundance of the integral membrane protein synaptophysin in synaptic ve sicles and its multiple possible functional contributions to transmitter ex ocytosis and synaptic vesicle formation stand in sharp contrast to the obse rved lack of defects in synaptophysin knockout mice. Assuming that deficien cies are compensated by the often coexpressed synaptophysin isoform synapto porin, 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 pate-appearing photoreceptors, as seen by e lectron microscopy, possess reduced cytoplasmic electron density, swollen m itochondria, an enlarged cell surface area, and, most importantly, a signif icantly reduced number of synaptic vesicles with an unusually bright interi or, Quantification of the number of synaptic vesicles per unit area, not on ly in these, but also in all other rod terminals of knockout animals, revea ls a considerable reduction in vesicles that is even more pronounced during the dark period, i.e., at times of highest synaptic activity, Moreover. ac tivity-dependent reduction in synaptic vesicle diameter, typically occurrin g in wild-type mice, is not detected in knockout animals. The large number of clathrin-coated pits and vesicles in dark-adapted synap tophysin knockout mice is taken as an indication of compensatory usage of s ynaptophysin-independent pathway(s), and. conversely. in view of the overal l reduction in the number of synaptic vesicles, as an indication for the pr esence of another synaptophysin-dependent synaptic vesicle recycling pathwa y. Our results provide in vivo evidence for the importance of the integral membrane protein synaptophysin for synaptic vesicle recycling and formation . (C), 2001 IBRO, Published by Elsevier Science Ltd. All rights reserved.