Journal article
β Subunit Reshuffling Modifies N- and P/Q-Type Ca2+Channel Subunit Compositions in Lethargic Mouse Brain
Molecular and cellular neurosciences, Vol.13(4), pp.293-311
04/1999
DOI: 10.1006/mcne.1999.0748
PMID: 10328888
Abstract
Neuronal voltage-dependent Ca2+channels are heteromultimers of α1, β, and α2δ subunits, and any one of five α1subunits (α1A-E) may associate with one of four β subunits (β1–4). The specific α1-β combination assembled determines single-channel properties, while variation in the proportion of each combination contributes to the functional diversity of neurons. The mouse mutant lethargic (lh) exhibits severe neurological defects due to a mutation that deletes the α1subunit interaction domain of the β4subunit. Since β subunits regulate critical α1subunit properties in heterologous expression systems, loss of β4in lethargic could dramatically alter channel localization and behavior unless β1–3subunits can be used as substitutesin vivo.Here we demonstrate increased steady-state associations of α1Aand α1Bwith the remaining β1–3subunits, without significant changes in β1–3mRNA abundance. The immunolocalization of α1Aand α1Bprotein in lethargic brain is indistinguishable from wild-type by light microscopy. Furthermore, the measurement of large-amplitude P-type currents in dissociated lethargic Purkinje neurons indicates that these α1A-containing channels retain regulation by β subunits. We conclude that several properties of α1Aand α1Bproteins are not uniquely regulated by β4in vivoand may be rescued by β1–3subunit reshuffling. The complex neurological manifestation of the lethargic mutation therefore emerges from loss of β4coupled with the widespread pairing of surrogate β subunits with multiple Ca2+channel subtypes. The existence of β subunit reshuffling demonstrates that molecular plasticity of Ca2+channel assembly, a normal feature of early brain development, is retained in the mature brain.
Details
- Title: Subtitle
- β Subunit Reshuffling Modifies N- and P/Q-Type Ca2+Channel Subunit Compositions in Lethargic Mouse Brain
- Creators
- Daniel L Burgess - Department of Neurology, Baylor College of Medicine, Houston, Texas, 77030Gloria H Biddlecome - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa, 52242Stefan I McDonough - Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, 02115Maria E Diaz - Department of Neurology, Baylor College of Medicine, Houston, Texas, 77030Carolyn A Zilinski - Department of Neurology, Baylor College of Medicine, Houston, Texas, 77030Bruce P Bean - Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, 02115Kevin P Campbell - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa, 52242Jeffrey L Noebels - Department of Neurology, Baylor College of Medicine, Houston, Texas, 77030
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular neurosciences, Vol.13(4), pp.293-311
- Publisher
- Elsevier Inc
- DOI
- 10.1006/mcne.1999.0748
- PMID
- 10328888
- ISSN
- 1044-7431
- eISSN
- 1095-9327
- Language
- English
- Date published
- 04/1999
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020782502771
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