Lack of CaBP1/caldendrin or CaBP2 leads to altered ganglion cell responses

Abstract

Calcium-binding proteins (CaBPs) form a subfamily of calmodulin-like proteins that were cloned from the retina. CaBP4 and CaBP5 have been shown to be important for normal visual function.

Although CaBP1/caldendrin and CaBP2 have been shown to modulate various targets in vitro, it is not known if they contribute to the transmission of light responses through the retina. Therefore, we generated mice that lack CaBP2 or CaBP1/caldendrin (Cabp2^-/- and Cabp1^-/-) to test if these CaBPs are essential for normal retinal function. By immunohistochemistry, the overall morphology of Cabp1^-/- and Cabp2^-/- retinas and the number of synaptic ribbons appear normal; transmission electron microscopy shows normal tethered ribbon synapses and synaptic vesicles as in wild-type retina. However, whole-cell patch clamp recordings showed that light responses of retinal ganglion cells of Cabp2^-/- and Cabp1 ^-/- mice differ in amplitude and kinetics from those of wild-type mice. We conclude that CaBP1/caldendrin and CaBP2 are not required for normal gross retinal and synapse morphology but are necessary for the proper transmission of light responses through the retina; like other CaBPs, CaBP1/caldendrin and CaBP2 likely act by modulating presynaptic Ca²⁺-dependent signaling mechanisms.

Significance Statement: Electrical signals generated by the photoreceptors in response to incident light are processed by diverse retinal neurons before being sent to the brain. Ca²⁺ signaling controls both cellular and synaptic mechanisms that shape signals as they are transmitted through the retina. Ca²⁺-binding proteins, including the calmodulin-like CaBPs, exert Ca²⁺-dependent effects on specific target proteins—e.g. ion channels. To determine whether CaBP1/caldendrin and CaBP2 are important for normal retinal function, we took advantage of CaBP1/caldendrin and CaBP2 deficient mice. Although these proteins are not required for retinal development and maintenance, CaBP1/caldendrin and CaBP2 are important for normal transfer of light signals through the retina.