Stac1 Regulates Sensory Stimulus Induced Escape Locomotion

Abstract

The stac family of genes are expressed by several cell types including neurons and muscles in a wide variety of animals. In vertebrates, stac3 encodes an adaptor protein specifically expressed by skeletal muscle that regulates L-type calcium channels (CaChs) and excitation-contraction coupling. The function of Stac proteins expressed by neurons in the vertebrate CNS, however, is unclear. To better understand neuronal Stac proteins, we identified the stac1 gene in zebrafish. stac1 is expressed selectively in the embryonic CNS including in Kolmer-Agduhr (KA) neurons, the cerebral fluid-contacting neurons (CSF-cNs) in the spinal cord. Previously CSF-cNs in the spinal cord were implicated in locomotion by zebrafish larvae. Thus, expression of stac1 by CSF-cNs and the regulation of CaChs by Stac3 suggest the hypothesis that Stac1 may be important for normal locomotion by zebrafish embryos. We tested to see if optogenetic activation of CSF-cNs was sufficient to induced swimming in embryos as it is in larvae. Indeed, optogenetic activation of CSF-cNs in embryos induced swimming in embryos. Next, we generated stac1-/- null embryos and found that both mechanosensory and noxious stimulus-induced swimming were decreased. We further found that zebrafish embryos respond more vigorously to tactile stimulation in the light compared to the dark. Interestingly, light enhancement of touch-induced swimming was eliminated in stac1 mutants. Thus, Stac1 regulates escape locomotion in zebrafish embryos perhaps by regulating the activity of CSF-cNs. SIGNIFICANCE STATEMENTThe stac genes are a small family of genes found in neurons and muscle in both vertebrates and invertebrates. Stac3 is a muscle protein that controls excitation-contraction coupling via regulation of L-type calcium channels and in humans a STAC3 mutation is responsible for a congenital myopathy. The function of neural Stac proteins, however, is unknown in vertebrates. The findings of this report show that neural stac1 is expressed by cerebral fluid-contacting neurons (CSF-cNs) in the spinal cord of zebrafish embryos and that it is necessary for normal sensory stimulus induced escape swimming. To our knowledge this is the first demonstration of a function for stac genes in neurons in the vertebrate nervous system.