A CaMK IV responsive RNA element mediates depolarization-induced alternative splicing of ion channels

Nature ◽  
2001 ◽  
Vol 410 (6831) ◽  
pp. 936-939 ◽  
Author(s):  
Jiuyong Xie ◽  
Douglas L. Black
Keyword(s):  
Alternative Splicing ◽  
Ion Channels ◽  
Camk Iv

scholarly journals Alternative Splicing of a Protein Domain Indispensable for Function of Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channels

2012 ◽  
Vol 287 (44) ◽  
pp. 36663-36672 ◽  
Author(s):  
Julia Frühwald ◽  
Julia Camacho Londoño ◽  
Sandeep Dembla ◽  
Stefanie Mannebach ◽  
Annette Lis ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Protein Domain ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

scholarly journals Alternative Splicing Switches the Divalent Cation Selectivity of TRPM3 Channels

2005 ◽  
Vol 280 (23) ◽  
pp. 22540-22548 ◽  
Author(s):  
Johannes Oberwinkler ◽  
Annette Lis ◽  
Klaus M. Giehl ◽  
Veit Flockerzi ◽  
Stephan E. Philipp
Keyword(s):  
Alternative Splicing ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Splice Variants ◽  
Large Family ◽  
Ionic Selectivity ◽  
Pore Region ◽  
Cation Selectivity ◽  
Ion Conducting

TRPM3 is a poorly understood member of the large family of transient receptor potential (TRP) ion channels. Here we describe five novel splice variants of TRPM3, TRPM3α1–5. These variants are characterized by a previously unknown amino terminus of 61 residues. The differences between the five variants arise through splice events at three different sites. One of these splice sites might be located in the pore region of the channel as indicated by sequence alignment with other, better-characterized TRP channels. We selected two splice variants, TRPM3α1 and TRPM3α2, that differ only in this presumed pore region and analyzed their biophysical characteristics after heterologous expression in human embryonic kidney 293 cells. TRPM3α1 as well as TRPM3α2 induced a novel, outwardly rectifying cationic conductance that was tightly regulated by intracellular Mg2+. However, these two variants are highly different in their ionic selectivity. Whereas TRPM3α1-encoded channels are poorly permeable for divalent cations, TRPM3α2-encoded channels are well permeated by Ca2+ and Mg2+. Additionally, we found that currents through TRPM3α2 are blocked by extracellular monovalent cations, whereas currents through TRPM3α1 are not. These differences unambiguously show that TRPM3 proteins constitute a pore-forming channel subunit and localize the position of the ion-conducting pore within the TRPM3 protein. Although the ionic selectivity of ion channels has traditionally been regarded as rather constant for a given channel-encoding gene, our results show that alternative splicing can be a mechanism to produce channels with very different selectivity profiles.

TRPM3, a biophysical enigma?

2007 ◽  
Vol 35 (1) ◽  
pp. 89-90 ◽  
Author(s):  
J. Oberwinkler
Keyword(s):  
Alternative Splicing ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Sodium Concentration ◽  
Pore Region ◽  
Bivalent Cations ◽  
Transient Receptor Potential Melastatin ◽  
Ion Conducting ◽  
Transient Receptor

TRPM3 [TRP (transient receptor potential) melastatin 3] is one of the least investigated proteins of the TRP family of ion channels. Heterologously expressed TRPM3 channels are constitutively active, have an outwardly rectifying current–voltage relationship and are inhibited by intracellular Mg2+ ions. Besides these rather common features, in which TRPM3 channels resemble the closely related channels TRPM6 and TRPM7, TRPM3 channels have several unique characteristics. The TRPM3 gene encodes a plethora of different proteins owing to alternative splicing and alternative exon usage. One site of alternative splicing affects the ion-conducting pore region and profoundly alters the pore properties of the encoded channels. The channels having the longer pore region efficiently conduct univalent cations, but are only poorly permeated by bivalent cations. Conversely, the channels with the shorter pore region are highly permeable to bivalent cations. Unusually, the short-pore TRPM3 channels are inhibited by extracellular Na+ ions. At physiological sodium concentration, this block is very strong, making it difficult to envision a physiological function for these ion channels. Recently, pharmacological investigations have been initiated in order to identify substances that influence TRPM3 channel activity. With the use of such substances, it might be possible to identify TRPM3 channels in their native environment and to elucidate some of their physiological roles. Hopefully, TRPM3 channels will then no longer appear to be as enigmatic as they do right now.

Gephyrin: does splicing affect its function?

2006 ◽  
Vol 34 (1) ◽  
pp. 45-47 ◽  
Author(s):  
I. Paarmann ◽  
T. Saiyed ◽  
B. Schmitt ◽  
H. Betz
Keyword(s):  
Alternative Splicing ◽  
Ion Channels ◽  
Single Cells ◽  
Protein Structures ◽  
Cell Types ◽  
Binding Partners ◽  
Its Gene ◽  
Substantial Progress ◽  
Different Cell Types ◽  
Made In

Gephyrin is a protein involved in both synaptic anchoring of inhibitory ligand-gated ion channels and molybdenum cofactor synthesis. Substantial progress has been made in understanding its gene and protein structures. Furthermore, numerous binding partners of gephyrin have been identified. The mechanisms by which these interactions occur are unclear at present. Alternative splicing has been proposed to contribute to gephyrin's functional diversity within single cells as well as in different cell types and tissues.

Linking transcription, RNA polymerase II elongation and alternative splicing

2020 ◽  
Vol 477 (16) ◽  
pp. 3091-3104 ◽  
Author(s):  
Luciana E. Giono ◽  
Alberto R. Kornblihtt
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Rna Polymerase Ii ◽  
Environmental Changes ◽  
Transcription Elongation ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Stepping Stones ◽  
Eukaryotic Transcription

Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic — such as promoter structure — and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.

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