Table of Contents

December 2002; 2 (8)



  • The activity of some voltage-gated calcium channels (VGCCs) can be inhibited by specific G protein β subunits. Conversely, in the case of N-type VGCCs, protein kinase C can relieve Gβ-dependent inhibition by phosphorylating at least one specific site on the calcium channel. A recent publication describes a newly identified method of intracellular regulation of specific VGCCs. Wu et al. have uncovered that VGCC activity can be regulated by phosphatidylinositol-4′,5′-bisphosphate (PIP2 ). Whereas PIP2 is important for maintaining the activity (open state) of Cav2.1 (N-type) and Cav2.2 (P/Q-type) channels, the enzymatic breakdown of PIP2 leads to the inactivation of these channels. Additionally, PIP2 can cause changes in voltage-dependent activation of Cav2.2 (P/Q-type) channels that make it more difficult for these channels to open (from the closed state). Furthermore, protein kinase A activity can circumvent PIP2-mediated inhibition. Thus, the PIP2-mediated regulation of VGCCs is tightly controlled by the functions of kinases (and phosphatases), as well as phospholipases. Wu et al. stress that because PIP2 can be found at synapses, PIP2-dependent control of VGCCs “could have profound consequences on synaptic transmission and plasticity.”

  • The family of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, collectively known as statins, is used clinically to reduce cholesterol levels in patients. Recent reports suggest that not only would statin therapy be beneficial for at-risk (genetically predisposed) people without symptoms of hypercholesterolemia, but that statins may have beneficial, pleiotropic effects in the treatment of autoimmune diseases. Youssef et al. have described how an HMG-CoA inhibitor, atorvastatin, might ameliorate experimental autoimmune encephalomyelitis (EAE), the mouse model for human multiple sclerosis. The possible clinical use of statins as anti-inflammatory drugs has also been demonstrated in other published reports. These provocative results suggest a role for statins in relieving autoimmune diseases such as multiple sclerosis.

  • Normally, cell division leads to shortening of telomeres, the nucleoprotein complexes located at the ends of linear chromosomes. When telomeres reach a critically short length, cells cease to divide. However, immortal tumor cells display stable telomere lengths and are able to maintain their proliferative state. Wong and colleagues have found that telomerase is sequestered by nucleoli during certain stages of the cell cycle, decreasing the likelihood of telomerase access to chromatin until the late S phase. Additionally, they demonstrate that ionizing radiation tends to keep telomerase sequestered in nucleoli, whereas cell transformation leads to telomerase translocation into the nucleoplasm, where, presumably, it can catalyze the lengthening of telomeres at appropriate and inappropriate sites. The sequestration of telomerase thus imposes a newly identified level of regulation on telomerase activity, implicating telomerase localization as a potentially useful target for pharmacotherapy.


  • Circadian rhythms allow organisms to optimize particular behaviors with regard to the time of day. The molecular mechanisms that account for the nightlife of mice, and the working day of humans, rest on light-dependent oscillations in the expression of specific proteins. Chief among these are the cryptochromes, proteins that absorb blue light and appear to act as photoreceptors in the circadian rhythms of humans and mice, as well as in plants, where cryptochromes were first discovered. Research into the brain’s clockwork has recently received new impetus, based on an appreciation that the circadian rhythm is germane not only to disturbances of mood and sleep cycles, but also to pharmacological interventions into disease states such as cancer.

  • By age thirty-five, one in four Americans is obese. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is secreted by the stomach and stimulates food intake. Ghrelin accomplishes this by facilitating growth hormone secretion and by transducing signals to hypothalamic regulatory nuclei that control energy homeostasis. Hosoda and colleagues review what is known about the molecular mechanisms by which ghrelin regulates hunger, satiety, and obesity. Understanding how ghrelin regulates the sensation or perception of hunger may yield promising future therapies for appetite control and overcoming anorexic behavior.


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