The Journal of Neuroscience, May 10, 2006, 26(19)
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This Week in The Journal
This Week in The Journal
Cellular/Molecular
The Cytoskeleton and the Paranode
Yasuhiro Ogawa, Dorothy P. Schafer, Ido Horresh, Vered Bar, Kimberly Hales, Yang Yang, Keiichiro Susuki, Elior Peles, Michael C. Stankewich, and Matthew N. Rasband
(see pages 52305239)
Paranodal junctions that flank nodes of Ranvier contain a cytoskeleton specialized to prevent membrane protein diffusion in and out of the nodes. This week Ogawa et al. used three known paranodal cell adhesion molecules to fish out additional paranodal molecules. As starting material, the authors isolated optic nerve membranes enriched in glial protein NF155 and the axonal proteins Caspr and contactin. Of 51 molecules identified by liquid chromatographytandem mass spectrometry,
II spectrin,
II spectrin, and ankyrinB cofractionated with Caspr as part of a paranodal complex. These proteins also associated with protein 4.1B. Immunostaining revealed these cytoskeletal proteins at paranodes in the central and peripheral nervous system. An enzymatic treatment that caused myelin retraction from the axon left
II spectrin and ankyrinB staining intact, identifying them as axonal proteins. AnkyrinB localization required Caspr, but not the juxtaparanodal protein Caspr2, indicating that paranodal axonglia interactions are required for formation of the paranodal cytoskeleton.
Development/Plasticity/Repair
Lining Up the Hair Cells
Mireille Montcouquiol, Nathalie Sans, David Huss, Jacob Kach, J. David Dickman, Andrew Forge, Rivka A. Rachel, Neal G. Copeland, Nancy A. Jenkins, Debora Bogani, Jennifer Murdoch, Mark E. Warchol, Robert J. Wenthold, and Matthew W. Kelley
(see pages 52655275)
How is it that cells in an epithelial sheet line up with the same orientation? In this week's Journal, Montcouquiol et al. examine some of the proteins involved in this planar cell polarity (PCP) problem in the mammalian system that perhaps best illustrates the process: cochlear hair cells. Mutations in mice have led to the identification of Vangl2, Scrb1, and Celsr1 as genes integral to PCP. Here the authors raised an antibody to Vangl2 and demonstrated its asymmetric expression at cellcell boundaries between cochlear hair and support cells. In looptail mice that harbor a mutation in Vangl2, polarization failed in the cochlea and in vestibular sensory epithelium. A yeast two-hybrid screen revealed an interaction between the postsynaptic density/Discs large/zona occludens 1 (PDZ)-binding domain of Vangl2 and PDZ domains in Scrb1. Celsr1 was required for Vangl2 asymmetry. The authors also identified Fz3 that was asymmetrically localized in cochlear cells and depended upon Vangl2 expression.

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The schema illustrates proposed interactions between paranodal cell adhesion molecules and paranodal cytoskeletal proteins. See the article by Ogawa et al. for details.
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Behavioral/Systems/Cognitive
Calming an "ADHD" Mouse
Kazuhiro Tanaka, Norihito Shintani, Hitoshi Hashimoto, Naofumi Kawagishi, Yukio Ago, Toshio Matsuda, Ryota Hashimoto, Hiroshi Kunugi, Akiko Yamamoto, Chihiro Kawaguchi, Takeshi Shimada, and Akemichi Baba
(see pages 50915097)
The paradoxical therapeutic actions of psychostimulant drugs in people with attention deficit and hyperactivity disorder (ADHD) are still mysterious. This week, Tanaka et al. shed some light on this question in mice lacking Adcyap1, the gene that encodes PACAP (pituitary adenylate cyclase-activating polypeptide). These mice are hyperlocomotive and have deficits in prepulse inhibition (PPI), a measure of sensorimotor gating in which a weak acoustic stimulus reduces the subsequent reaction to a startling stimulus. In the Adcyap1/ mouse, amphetamine normalized PPI responses and diminished hyperlocomotive behavior. Although the dopamine receptor antagonist haloperidol had no effect on PPI, a 5-HT1A receptor antagonist blocked the antihyperkinetic effect of amphetamine. There also was an amphetamine-induced increase in activity in prefrontal cortex as measured by c-Fos labeling. Although not quite an animal model of ADHD, the Adcyap1/ mouse may help explain the antihyperkinetic effect of psychostimulants.
Neurobiology of Disease
Lighting up ApoE Expression Patterns
Qin Xu, Aubrey Bernardo, David Walker, Tiffany Kanegawa, Robert W. Mahley, and Yadong Huang
(see pages 49854994)
Amyloid plaques and neurofibrillary tangles of Alzheimer's disease (AD) contain apolipoprotein E (apoE), the
4 allele of which considerably increases risk for late-onset AD. An individual with two
4 alleles has a 5090% chance of developing AD by age 85. To track the expression pattern of apoE in brain, Xu et al. created EGFPapoE reporter mice by expressing enhanced green fluorescent protein (EGFP) on one apoE allele and leaving the other allele functionally intact. As expected, hepatocytes and macrophages expressed high levels of apoE. Approximately 75% of astrocytes expressed apoE under normal conditions, and even after kainic acid-induced injury, a subset did not express EGFP. In contrast, only a small minority of activated microglia expressed EGFP. Hippocampal neurons expressed EGFP only after injury with kainic acid. Smooth muscle cells of large blood vessels, cells surrounding small vessels, and cells of the choroid plexus also expressed apoE.
DOI:
Related articles in J. Neurosci.:
- Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus
- Qin Xu, Aubrey Bernardo, David Walker, Tiffany Kanegawa, Robert W. Mahley, and Yadong Huang
J. Neurosci. 2006 26: 4985-4994.
[Abstract]
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- Psychostimulant-Induced Attenuation of Hyperactivity and Prepulse Inhibition Deficits in Adcyap1-Deficient Mice
- Kazuhiro Tanaka, Norihito Shintani, Hitoshi Hashimoto, Naofumi Kawagishi, Yukio Ago, Toshio Matsuda, Ryota Hashimoto, Hiroshi Kunugi, Akiko Yamamoto, Chihiro Kawaguchi, Takeshi Shimada, and Akemichi Baba
J. Neurosci. 2006 26: 5091-5097.
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- Spectrins and AnkyrinB Constitute a Specialized Paranodal Cytoskeleton
- Yasuhiro Ogawa, Dorothy P. Schafer, Ido Horresh, Vered Bar, Kimberly Hales, Yang Yang, Keiichiro Susuki, Elior Peles, Michael C. Stankewich, and Matthew N. Rasband
J. Neurosci. 2006 26: 5230-5239.
[Abstract]
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- Asymmetric Localization of Vangl2 and Fz3 Indicate Novel Mechanisms for Planar Cell Polarity in Mammals
- Mireille Montcouquiol, Nathalie Sans, David Huss, Jacob Kach, J. David Dickman, Andrew Forge, Rivka A. Rachel, Neal G. Copeland, Nancy A. Jenkins, Debora Bogani, Jennifer Murdoch, Mark E. Warchol, Robert J. Wenthold, and Matthew W. Kelley
J. Neurosci. 2006 26: 5265-5275.
[Abstract]
[Full Text]