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The Journal of Neuroscience, December 10, 2008, 28(50)

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This Week in The Journal
This Week in The Journal

Cellular/Molecular

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

(see pages 13435–13447)

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, RIM1, encodes a previously undiscovered second isoform, RIM1β. RIM1 has several protein-interaction domains that enable it to bind several other active-zone proteins. RIM1β lacks the N-terminal protein interaction domain of RIM1, but is otherwise identical. RIM1 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 RIM1 appears to be involved in protein-kinase-A-dependent presynaptic long-term plasticity.

Development/Plasticity/Repair

Crk and CrkL Mediate Reelin Signaling

Tae-Ju Park and Tom Curran

(see pages 13551–13562)

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.

View larger version (79K): [in this window] [in a new window]   Knock-out of Crk and CrkL in mouse neurons (right) disrupts foliation and layering in the cerebellum. See the article by Park and Curran for details.

 
Behavioral/Systems/Cognitive

Estradiol Decreases Cortical Functional Lateralization

Susanne Weis, Markus Hausmann, Barbara Stoffers, René Vohn, Thilo Kellermann, and Walter Sturm

(see pages 13401–13410)

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.

Neurobiology of Disease

Near-Infrared Light Protects Retinas from Mitochondrial Damage

Julio C. Rojas, Jung Lee, Joseph M. John, and F. Gonzalez-Lima

(see pages 13511–13521)

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.

Related articles in J. Neurosci.:

Estradiol Modulates Functional Brain Organization during the Menstrual Cycle: An Analysis of Interhemispheric Inhibition

Susanne Weis, Markus Hausmann, Barbara Stoffers, René Vohn, Thilo Kellermann, and Walter Sturm
J. Neurosci. 2008 28: 13401-13410. [Abstract] [Full Text]  

RIM1 and RIM1β Are Synthesized from Distinct Promoters of the RIM1 Gene to Mediate Differential But Overlapping Synaptic Functions

Pascal S. Kaeser, Hyung-Bae Kwon, Chiayu Q. Chiu, Lunbin Deng, Pablo E. Castillo, and Thomas C. Südhof
J. Neurosci. 2008 28: 13435-13447. [Abstract] [Full Text]  

Neuroprotective Effects of Near-Infrared Light in an In Vivo Model of Mitochondrial Optic Neuropathy

Julio C. Rojas, Jung Lee, Joseph M. John, and F. Gonzalez-Lima
J. Neurosci. 2008 28: 13511-13521. [Abstract] [Full Text]  

Crk and Crk-Like Play Essential Overlapping Roles Downstream of Disabled-1 in the Reelin Pathway

Tae-Ju Park and Tom Curran
J. Neurosci. 2008 28: 13551-13562. [Abstract] [Full Text]  

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content

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