Abstract
Purpose: :
Phosphatidylinositol (3,4,5)-triphosphate-dependent Rac Exchanger 2 (P-Rex2) is a guanine nucleotide exchange factor (GEF) for Rac GTPases, which are key regulators of the actin cytoskeleton and have important roles in regulating development of neuronal processes and architecture. To better understand mechanisms potentially regulating the development of neuronal and synaptic architecture in the retina, we investigated the distribution of P-Rex2 in the cells and synapses of the mouse retina.
Methods: :
Expression and localization of P-Rex2 in the mouse retina was assessed by immunohistochemical labeling for P-Rex2 or P-Rex2 in combination with known markers for specific retinal cell types and synapses.
Results: :
P-Rex2 labeling was restricted to the outer and inner plexiform layers of the retina (OPL and IPL, respectively), suggesting synaptic localization. Double labeling for P-Rex2 and the ribbon synapse marker VGluT1 showed that P-Rex2 was expressed specifically in the glutamatergic ribbon synapses of photoreceptors and bipolar cells. Double labeling for P-Rex2 and peanut agglutinin, a cone marker, showed that P-Rex2 was expressed in the terminals of both rod and cone photoreceptors. P-Rex2 was also expressed in the terminals of rod bipolar cells, and OFF- and ON-cone bipolar cell types. In contrast, P-Rex2 showed little or no colocalization with markers for amacrine cells or their conventional synapses. In the developing retina, P-Rex2 was expressed in developing photoreceptor terminals by postnatal day 8 (P8), a time when photoreceptors are actively establishing synaptic contacts. In contrast, little labeling for P-Rex2 was present in the developing IPL at P8, but was present by the time of eye opening at P14/15.
Conclusions: :
P-Rex2 is expressed specifically in ribbon synaptic terminals of photoreceptors and bipolar cells. The expression of P-Rex2 is positioned spatially and temporally to regulate development and/or plasticity of photoreceptor and bipolar cell ribbon synapse, presumably by modulating cytoskeletal remodeling via Rac GTPases.
Keywords: retinal development • synapse • retina: distal (photoreceptors, horizontal cells, bipolar cells)