Lack of CaBP1/Caldendrin or CaBP2 Leads to Altered Ganglion Cell Responses.
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 targetsin vitro, it is not known whether they contribute to the transmission of light responses through the retina. Therefore, we generated mice that lack CaBP2 or CaBP1/caldendrin (Cabp2-/-andCabp1-/-) to test whether these CaBPs are essential for normal retinal function. By immunohistochemistry, the overall morphology ofCabp1-/-andCabp2-/-retinas and the number of synaptic ribbons appear normal; transmission electron microscopy shows normal tethered ribbon synapses and synaptic vesicles as in wild-type retinas. However, whole-cell patch clamp recordings showed that light responses of retinal ganglion cells ofCabp2-/-andCabp1-/-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.
Department of Physiology and Biophysics, Howard Hughes Medical Institute, University of Washington , Seattle, WA 98195.
Raunak
R
Sinha
Departments of Molecular Physiology and Biophysics, Otolaryngology Head-Neck Surgery, and Neurology, University of Iowa , Iowa City, IA 52242.
Amy
A
Lee
Department of Physiology and Biophysics, Howard Hughes Medical Institute, University of Washington , Seattle, WA 98195.
Fred
0000-0002-1052-2609
F
Rieke
Department of Physiology and Biophysics, University of Washington , Seattle, WA 98195.
Françoise
0000-0003-1887-1798
F
Haeseleer
D000200:Action Potentials; D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D051245:Retinal Bipolar Cells / Q000378:metabolism / Q000648:ultrastructure; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D046509:Tissue Culture Techniques; D014785:Vision, Ocular / Q000502:physiology
D002135:Calcium-Binding Proteins; C085578:Ca-binding protein 2; C085577:Ca2+-binding protein-1
bipolar cells; calcium-binding proteins; ganglion cells; knockout mice; light response; retina