Serca isoform expression in the mammalian retina

Abstract

The sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA) is a key intracellular calcium transporter, which regulates cellular calcium concentration [Ca 2+ ] by transporting Ca 2+ ions from the cytosol into the endoplasmic reticulum. SERCA-mediated Ca 2+ sequestration controls proper folding of newly synthesized proteins within the ER as well as the timing and spatial patterning of depolarization-evoked Ca 2+ responses in the cytoplasm. We studied expression and distribution of all three SERCA isoforms in the mouse retina using isoform-specific antibodies. No immunostaining was observed with the SERCA1 antibody. SERCA2 was expressed in photoreceptor inner segments, amacrine and ganglion cells of the mouse retina. Similar SERCA2 localization was observed in adult rat, macaque and ground squirrel retinas. Analysis of distribution of SERCA2 immunofluorescence in the developing mouse retina revealed prominent SERCA2 signals throughout postnatal development. The antibody raised against the SERCA3 isoform labeled inner segments of photoreceptors and cell bodies in the inner nuclear layer of the mouse retina. The SERCA3 signal was detected in the inner plexiform layer of the early postnatal retina, but moved by P10 to the outer retina where it was concentrated in outer segments of cones. These results indicate that SERCA2 represents the dominant SERCA isoform in the mammalian retina. SERCA3 may contribute to calcium regulation in photoreceptors and bipolar cells.

OPA1, the disease gene for optic atrophy type Kjer, is expressed in the inner ear

“…Measurements of otoacoustic emissions were normal in the analyzed cases (AmatiBonneau et al 2003(AmatiBonneau et al , 2005. The clinical data of some cases agree with the diagnostic criteria of auditory neuropathy (Amati-Bonneau et al 2003, 2005. The primary lesion in auditory neuropathy can be located to the inner hair cells (IHC), the auditory nerve, or the synapses between them (Cone-Wesson et al 2000;Starr et al 2000).…”

“…Association of moderate bilateral loss of hearing thresholds with a speciWc mutation (R445H) in the OPA1 gene was recently discovered (Amati-Bonneau et al 2003, 2005Shimizu et al 2003;Payne et al 2004;Li et al 2005). Recently, the incorporation of a speciWc mutation (c.1065 + 5G!A) in the OPA1 gene in a mouse model did not indicate any loss of hearing function (Alavi et al 2007) emphasizing necessity for a better understanding of OPA1 gene expression in the inner ear and the analyses of other mouse models carrying mutations in OPA1.…”

“…3f, 7d, e), where mitochondria are located in the Hensen's body. Mitochondria provide ATP for multiple cellular functions, including for example Ca 2+ -ATPases (PMCA, SERCA) (Dumont et al 2001;Krizaj 2005), which extrude Ca 2+ after hair cell stimulation from the cytoplasm. Regeneration of tip-links after stimulation was shown to be dependent on Ca 2+ -extrusion (Zhao et al 1996).…”

“…There are, however, several cases of optic atrophy associated with sensorineural hearing loss (Hoyt 1980;Treft et al 1984). It has been shown recently that the R445H mutation of OPA1, altering a highly conserved residue in the GTPase domain, is involved in adOA and moderate progressive hearing loss (adOAD) or in a more complex syndrome including adOA, hearing loss, ptosis and ophthalmoplegia (Amati-Bonneau et al 2003, 2005Shimizu et al 2003;Payne et al 2004;Li et al 2005).…”

Determination of apparent calcium affinity for endogenously expressed human sarco(endo)plasmic reticulum calcium-ATPase isoform SERCA3

“…The highest SERCA3 expression is observed in cells of hematopoietic lineage (platelets, mast cells, and lymphocytes), embryologically related endothelial cells, secretory epithelial cells (large and small intestine, thymus, and trachea), and Purkinje neurons in the cerebellum (1,5,10,39,50). The expression of SERCA3 has also been detected in the mammalian retina and human myocardium (14,27). In addition, the expression of SERCA3 mRNA during ontogeny in the rat indicates a tissue-specific and developmentally regulated pattern in the cardiovascular system (2).…”