EML1 is essential for retinal photoreceptor migration and survival

Deepak Poria,Shimming Chen,Chi Sun,Andrea Santeford,Oleg G Kisselev,Vladimir J Kefalov,Rajendra S Apte,Michel Kielar

doi:10.1038/s41598-022-06571-3

Abstract

Calcium regulates the response sensitivity, kinetics and adaptation in photoreceptors. In striped bass cones, this calcium feedback includes direct modulation of the transduction cyclic nucleotide-gated (CNG) channels by the calcium-binding protein CNG-modulin. However, the possible role of EML1, the mammalian homolog of CNG-modulin, in modulating phototransduction in mammalian photoreceptors has not been examined. Here, we used mice expressing mutant Eml1 to investigate its role in the development and function of mouse photoreceptors using immunostaining, in-vivo and ex-vivo retinal recordings, and single-cell suction recordings. We found that the mutation of Eml1 causes significant changes in the mouse retinal structure characterized by mislocalization of rods and cones in the inner retina. Consistent with the fraction of mislocalized photoreceptors, rod and cone-driven retina responses were reduced in the mutants. However, the Eml1 mutation had no effect on the dark-adapted responses of rods in the outer nuclear layer. Notably, we observed no changes in the cone sensitivity in the Eml1 mutant animals, either in darkness or during light adaptation, ruling out a role for EML1 in modulating cone CNG channels. Together, our results suggest that EML1 plays an important role in retina development but does not modulate phototransduction in mammalian rods and cones.

Highlights

Calcium regulates the response sensitivity, kinetics and adaptation in photoreceptors
A relatively less studied aspect of this calcium feedback is the direct modulation of the cyclic nucleotidegated (CNG) channels in the plasma membrane of rod and cone photoreceptors
We examined the expression of Eml[1] in the Nrl knockout (Nrl−/−) retina, which lacks rods and is populated exclusively by cone-like photoreceptors[14]

Summary

Introduction

Calcium regulates the response sensitivity, kinetics and adaptation in photoreceptors. In striped bass, a novel protein termed CNG-modulin was shown to directly modulate the transduction CNG channels in c ones[9] and later in zebrafish cones its homolog Eml[1] (echinoderm microtubule associated protein 1 (EMAP1)-like), was shown to modulate these channels[10] Based on these findings, we hypothesized that EML1 may play a role in the modulation of CNG channels in mammalian photoreceptors. In the course of the preparation of this paper, another group published a study using an unrelated Eml[1] mutant causing a loss of the short length splice of the gene that affected the localization of photoreceptors in the developing mouse retina[12]. It appears that loss of either the full length or the short splice form of Eml[1] disrupts photoreceptor migration and survival

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Conclusion