1. Two RIM1 Isoforms Are Present in Active Zones
Pascal S. Kaeser, Hyung-Bae Kwon, Chiayu Q. Chiu, Lunbin Deng, Pablo E. Castillo, and Thomas C. Südhof
Presynaptic active zones comprise many proteins that help to ensure rapid neurotransmitter release near postsynaptic receptors, and modification of some of these proteins produces long-term potentiation or depression. Although most active-zone proteins have been assigned to a specific step in the release process (e.g., vesicle docking, priming, or fusion), the molecular mechanisms involved remain unknown, and additional proteins continue to be discovered. This week, Kaeser et al. report that the gene encoding an active-zone scaffolding protein, RIM1α, encodes a previously undiscovered second isoform, RIM1β. RIM1α has several protein-interaction domains that enable it to bind several other active-zone proteins. RIM1β lacks the N-terminal protein interaction domain of RIM1α, but is otherwise identical. RIM1α and RIM1β have largely overlapping expression patterns and functions. For example, both molecules appear to influence vesicle release probability at both excitatory and inhibitory synapses. But only RIM1α appears to be involved in protein-kinase-A-dependent presynaptic long-term plasticity.
2. Crk and CrkL Mediate Reelin Signaling
Tae-Ju Park and Tom Curran
Crk and CrkL are widely expressed adaptor proteins whose function is to bring together tyrosine-phosphorylated proteins and their downstream effectors. Crk and CrkL interact with many proteins and are involved in diverse biological process throughout the body. Park and Curran now suggest that Crk and CrkL are important components of the Reelin signaling cascade in neurons. Deletion of both Crk and CrkL specifically in developing neurons produced a phenotype nearly identical to that of reelin mutations. For example, layer formation, neuronal migration, and dendrite development were severely disrupted in the cerebellum, hippocampus, and cerebral cortex. Reelin, an extracellular secreted protein, binds to lipoprotein receptors, resulting in activation of tyrosine kinases that phosphorylate the protein Disabled-1. Disabled-1 then promotes phosphorylation of the kinase Akt. In Crk/CrkL double-knock-out mice, levels of phosphorylated Disabled-1 were comparable to wild-type, but Akt phosphorylation was reduced, placing Crk/CrkL between Disabled-1 and Akt in the Reelin signaling pathway.
3. Estradiol Decreases Cortical Functional Lateralization
Susanne Weis, Markus Hausmann, Barbara Stoffers, René Vohn, Thilo Kellermann, and Walter Sturm
The cerebral hemispheres are functionally specialized: the left hemisphere is generally dominant in verbal tasks, whereas the right hemisphere dominates in spatial tasks. This asymmetry is thought to depend on inhibition of the nondominant hemisphere by the dominant hemisphere. The degree of functional lateralization varies across individuals, and females tend to exhibit less asymmetry than males. Furthermore, functional cerebral asymmetries vary in women throughout menstrual cycles, and asymmetries in postmenopausal women are comparable to those in men, suggesting that sex hormones alter interhemispheric inhibition. To test this hypothesis, Weis et al. measured brain activity during a verbal task using functional magnetic resonance imaging in men and in women at two points of the menstrual cycle when estradiol levels differed. As predicted, active regions of the left hemisphere inhibited homotypic areas in the right hemisphere in men and in women when their estradiol levels were low, but the inhibition disappeared when estradiol levels were high.
4. Near-Infrared Light Protects Retinas from Mitochondrial Damage
Julio C. Rojas, Jung Lee, Joseph M. John, and F. Gonzalez-Lima
Near-infrared light therapy (NILT) increases survival of cultured neurons exposed to various stressors, improves behavioral recovery from stroke in rabbits, and speeds wound healing in humans. These effects are thought to be mediated by upregulation of mitochondrial proteins, endogenous antioxidants, and antiapoptotic proteins such as heat-shock proteins and Bcl-2. This week, Rojas et al. report that NILT greatly reduced retinal damage and associated behavioral deficits produced in rats by the mitochondrial toxin rotenone. NILT prevented rotenone-induced decreases in light sensitivity and greatly reduced thinning of the retinal layers. Interestingly, NILT increased activity of the mitochondrial respiratory protein cytochrome oxidase and of the antioxidant superoxide dismutase throughout the brain, suggesting that the infrared light can penetrate the skull (at least in rats) and induce neuroprotective effects in the brain. Because many neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis, involve mitochondrial dysfunction similar to that produced by rotenone, NILT may prove effective in treating these diseases as well.
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