Cabin1 expression suggests roles in neuronal development

Abstract

*Nervous system assembly and function depends on precise regulation of developmental gene expression. Cabin1, an essential gene in developing mice, is enriched in regions of the developing zebrafish central nervous system (CNS). Cabin1 is a repressor of MEF2-(myocyte enhancer factor 2) and calcineurin-mediated transcription in the immune system, but its function in the CNS during development is unknown. We identified Cabin1 from a library of genes enriched in developing neurons and determined the temporal and spatial expression of Cabin1 mRNA during CNS development. We found Cabin1 mRNA expression in the developing brain at times correlated with later aspects of neuronal differentiation. In some regions of the CNS Cabin1 expression overlaps with regions that also express proteins known to interact with Cabin1: MEF2 and/or calcineurin. We suggest that Cabin1 could act as a regulator of MEF2 and calcineurin activity in the developing nervous system, given their roles in neuronal differentiation and synaptic refinement. Developmental Dynamics 239:2443-2451,

Effects of embryonic cyclosporine exposures on brain development and behavior

“…Since calcineurin subunits are expressed in the developing brain and eye [31], we first examined if cyclosporine induces morphological defects in these organ systems. To examine the effects of cyclosporine on eye development, wild type embryos were exposed to 1, 2, 5 and 10 μM cyclosporine from 2-26 hpf and imaged at 3 dpf by standard bright-field microscopy.…”

“…It remains to be established if these effects are cell autonomous or if calcineurin signaling in other embryonic tissues influence development of the eye and brain. Calcineurin subunits are expressed in the developing brain and in the retina of the eye [31], suggesting that cell-autonomous processes might be important.…”

Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation

“…Therefore, RCAN1 would be responsible for the proper regulation of calcineurin signaling pathways, which is necessary for differentiation. Accordingly, Cabin1, another calcineurin regulator, is expressed in neurons undergoing axon growth and regulated synaptogenesis (56). Therefore, further characterization of the mechanisms by which RCAN1 controls neuronal differentiation may help to elucidate DS-related pathogeneses such as brain development, mental retardation, and Alzheimer disease.…”

Cabin1 localizes in glomerular podocyte and undergoes nuclear translocation during podocyte injury

“…9 Cabin1 is a natural selective inhibitor of CaN, it plays an important role in regulating cell functions by inhibiting CaN via its C-terminus. 10 As nuclear translocation of Cabin1 inhibited calcineurin-NFAT pathway during T-cell activation, 15 Cabin1 is likely translocate to nuclei in order to restrain calcineurin-NFAT pathway during podocyte injury. Targeted inhibition of CaN by Cabin1 has been showed in many studies.…”

“…Cabin1 extensively expresses in brain, heart, and other organs. 10,11 Cabin1 plays an important role in regulating cell functions by inhibiting CaN via its C-terminus. Downregulating Cabin1 expression sensitized human nasopharyngeal carcinoma cells to genotoxic drugs.…”