GRF1 and GRF2 (also known as RASGRF1 and RASGRF2, respectively) are guanine nucleotide exchange factors (GEFs) that are preferentially expressed in the central nervous system (CNS) where they activate small GTPases of the Ras or Rho/Rac family. Because GRF1 and GRF2 share a high structural homology and their expression patterns overlap, their respective discrete functions are unclear. In this study (p. ), Eugenio Santos and colleagues extend their previous findings of a role for GRF1 in visual processes and present a thorough analysis of the eye phenotypes of GRF1 and GRF2 knockdown in mice by using electroretinograhic assays and immunohistochemical analyses. First, they observed ectopic nuclei located in the photoreceptor segments of the retina of GRF2-knockout mice, which belong to cone photoreceptor cells and arise postnatally. The authors then go on to show that the regular nuclear migration of cones through the outer nuclear layer (ONL) towards photoreceptor segments is altered in the absence of GRF2, and, specifically the terminal movement of cone nuclei towards the outer limiting membrane (OLM). This migration defect results in a functional deficiency of the retina, as determined by a significant reduction in the response of cone cells in the absence of GRF2 compared to those of wild type. Furthermore, the authors describe the perinuclear accumulation of signalling factors involved in both nuclear migration and cytoskeletal organisation, pointing to a role of GRF2 in these processes that, however, requires further detailed investigation.
