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G. H. Grossman, S. A. Hagstrom; TULP1 Is Required for Normal Photoreceptor Synaptic Function. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1291. doi: https://doi.org/.
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Mutations in TULP1 cause of one form of autosomal recessive retinitis pigmentosa, a heterogeneous family of inherited retinal diseases. Tulp1 is found exclusively in photoreceptors, localizing in the inner segments, connecting cilium, perikarya and terminals. There is evidence that Tulp1 is essential for intracellular trafficking, and necessary for normal photoreceptor synaptic function. Previously, we reported that tulp1-/- mice develop early-onset, progressive photoreceptor degeneration, with involvement of both rods and cones. Recently, we demonstrated that Tulp1 interacts with Dynamin-1, a neuron-specific protein involved in synaptic vesicle transport and transmission at nerve terminals. To further investigate the consequence of Tulp1 deficiency on ribbon synapses, we utilized immunofluorescence to examine the morphology and distribution of several proteins specific to synaptic terminals in tulp1-/- mice as compared to wild-type mice.
Immunofluorescence was used to examine the morphology and distribution of several proteins specific to synaptic terminals in tulp1-/- mice as compared to wild-type mice.
We report that immuno-staining of 3 key cytomatrix scaffolding proteins associated with photoreceptor ribbon synapses; Ribeye, Bassoon and Piccolo, appear abnormal in the retina deficient of Tulp1. The hallmark horseshoe-shape ribbon structure is maintained in some tulp1-/- terminals; however, the majority of the terminals appear to have lost the normal close spatial relationship of these scaffolding proteins, and a less defined staining of both proteins is produced. In addition, Dynamin-1 staining appears aberrant in tulp1-/- mice, exhibiting a severe attenuation.
In sum, Tulp1 is a photoreceptor-synaptic protein as evidenced by the co-localization with the synaptic proteins Dynamin-1, Ribeye, Bassoon and Piccolo. There is substantial evidence indicating that the functional ribbon complex requires a tight coupling of these proteins. Our new data demonstrate that in tulp1-/- retinas, this tight spatial relationship between cytomatrix proteins is disrupted, and that synaptic function is abnormal, supporting our hypothesis that Tulp1 is a component of the molecular machinery required for normal photoreceptor synaptic function.
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