| Profiling the array of Ca(v)3.1 variants from the human T-type calcium channel gene CACNA1G: alternative structures, developmental expression, and biophysical variations. | |
| | |
MedLine Citation:
|
PMID: 16671074 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
We describe the regulated transcriptome of CACNA1G, a human gene for T-type Ca(v)3.1 calcium channels that is subject to extensive alternative RNA splicing. Fifteen sites of transcript variation include 2 alternative 5'-UTR promoter sites, 2 alternative 3'-UTR polyadenylation sites, and 11 sites of alternative splicing within the open reading frame. A survey of 1580 fetal and adult human brain full-length complementary DNAs reveals a family of 30 distinct transcripts, including multiple functional forms that vary in expression with development. Statistical analyses of fetal and adult transcript populations reveal patterns of linkages among intramolecular splice site configurations that change dramatically with development. A shift from nearly independent, biased splicing in fetal transcripts to strongly concerted splicing in adult transcripts suggests progressive activation of multiple "programs" of splicing regulation that reorganize molecular structures in differentiating cells. Patch-clamp studies of nine selected variants help relate splicing regulation to permutations of the gating parameters most likely to modify T-channel physiology in expressing neurons. Gating behavior reflects combinatorial interactions between variable domains so that molecular phenotype depends on ensembles of coselected domains, consistent with the observed emergence of concerted splicing during development. We conclude that the structural gene and networks of splicing regulatory factors define an integrated system for the phenotypic variation of Ca(v)3.1 biophysics during nervous system development. |
| | |
Authors:
|
Mark C Emerick; Rebecca Stein; Robin Kunze; Megan M McNulty; Melissa R Regan; Dorothy A Hanck; William S Agnew |
Related Documents
:
|
12595504 - Ofd1, the gene mutated in oral-facial-digital syndrome type 1, is expressed in the meta... 19749754 - Splice site strength-dependent activity and genetic buffering by poly-g runs. 10982344 - Overexpression of essential splicing factor asf/sf2 blocks the temporal shift in adenov... 15731334 - Targeted 'knockdown' of spliceosome function in mammalian cells. 9726364 - Modification of superoxide dismutase (sod) mrna and activity by a transient hypoxic str... 22536434 - Priority in selenium homeostasis involves regulation of sepsecs transcription in the ch... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Proteins Volume: 64 ISSN: 1097-0134 ISO Abbreviation: Proteins Publication Date: 2006 Aug |
Date Detail:
|
Created Date: 2006-06-22 Completed Date: 2006-08-02 Revised Date: 2008-11-21 |
Medline Journal Info:
|
Nlm Unique ID: 8700181 Medline TA: Proteins Country: United States |
Other Details:
|
Languages: eng Pagination: 320-42 Citation Subset: IM |
Copyright Information:
|
Copyright 2006 Wiley-Liss, Inc. |
Affiliation:
|
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Alternative Splicing Biophysics / methods Brain / embryology, metabolism Calcium Channels, T-Type / chemistry, physiology* DNA, Complementary / metabolism Gene Expression Regulation, Developmental* Genetic Variation Humans Kinetics Open Reading Frames Patch-Clamp Techniques Protein Conformation Protein Structure, Tertiary |
| Grant Support | |
ID/Acronym/Agency:
|
HL-R01-HL62603/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/CACNA1G protein, human; 0/Calcium Channels, T-Type; 0/DNA, Complementary |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Bilateral subthalamic nucleus deep brain stimulation improves certain aspects of postural control in...
Next Document: Learning and retention of movement sequences in Parkinson's disease.