The majority of multiexon mammalian genes contain alternatively spliced exons that have unique expression patterns in different cell populations and that have important cell functions. The expression profiles of alternative exons are controlled by cell-specific splicing factors that can promote exon inclusion or exon skipping but with few exceptions we do not know which specific splicing factors control the expression of alternatively spliced exons of known biological function. Many ion channel genes undergo extensive alternative splicing including that encodes the voltage-gated Ca2.
View Article and Find Full Text PDFSince President Richard Nixon declared a "War on Cancer" in 1971, the number of cancer survivors in the United States has quadrupled [1] and is still rising. Thanks to advance in cancer detection and treatment, the almost 15 million cancer survivors in the United States today could grow to some 19 million by 2024 [2]. Increasing survival rates have resulted in a shift: cancer is often treated as a chronic illness rather than a death sentence.
View Article and Find Full Text PDFWhen brothers Jamie and Glen Selby, aged 5 and 7, arrived at the Shriners Burns Institute in Denver, Colorado, in July 1983, more than 97% of their skin had been destroyed by a fire they had accidentally started while playing in an abandoned house. The boys were so badly burned that their outlook was grim-a 6-year-old friend who was also in the fire died from his injuries?but Jamie and Glen were lucky. Not only did they survive, but they were also some of the first patients to benefit from a new burn treatment nicknamed test-tube skin.
View Article and Find Full Text PDFTrends Neurosci
October 2013
Voltage-gated calcium ion (CaV) channels convert neuronal activity into rapid intracellular calcium signals to trigger a myriad of cellular responses. Their involvement in major neurological and psychiatric diseases, and importance as therapeutic targets, has propelled interest in subcellular-specific mechanisms that align CaV channel activity to specific tasks. Here, we highlight recent studies that delineate mechanisms controlling the expression of CaV channels at the level of RNA and protein.
View Article and Find Full Text PDFNeuronal voltage-gated calcium channels generate rapid, transient intracellular calcium signals in response to membrane depolarization. Neuronal Ca(V) channels regulate a range of cellular functions and are implicated in a variety of neurological and psychiatric diseases including epilepsy, Parkinson's disease, chronic pain, schizophrenia, and bipolar disorder. Each mammalian Cacna1 gene has the potential to generate tens to thousands of Ca(V) channels by alternative pre-mRNA splicing, a process that adds fine granulation to the pool of Ca(V) channel structures and functions.
View Article and Find Full Text PDFMany cellular processes are involved in optimizing protein function for specific neuronal tasks; here we focus on alternative pre-mRNA splicing. Alternative pre-mRNA splicing gives cells the capacity to modify and selectively re-balance their existing pool of transcripts in a coordinated way across multiple mRNAs, thereby effecting relatively rapid and relatively stable changes in protein activity. Here we report on and discuss the coordinated regulation of two sites of alternative splicing, e24a and e31a, in P-type CaV2.
View Article and Find Full Text PDFPeptide YY (PYY), a member of the NPY superfamily of peptides, is predominantly synthesized by the colon and is thought to act on both the gut and brain to modulate energy homeostasis. Although neurons expressing PYY mRNA have also been reported in the brainstem, little is known about their physiological role and study of their projections has been problematic due to crossreactivity of PYY antibodies with NPY. In the present study we examined the localization of central PYY cell bodies in the mouse, rat, and monkey.
View Article and Find Full Text PDFThe receptor subtypes that mediate the effects of neuropeptide Y (NPY) on food intake have not been clearly defined. The NPY Y4 receptor has been identified recently as a potential mediator of the regulation of food intake. The purpose of the present study was to characterize the central site of action of the Y4 receptor using a combination of neuroanatomical and physiological approaches.
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