Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel.

Neuron | 2018

Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating. Here, we report that voltage modulation of TMEM16A-CaCC involves voltage-dependent occupancy of calcium- and anion-binding site(s) within the membrane electric field as well as a voltage-dependent conformational change intrinsic to the channel protein. These gating modalities all critically depend on the sixth transmembrane segment.

Pubmed ID: 29478917 RIS Download

Research resources used in this publication

Antibodies used in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS069229
  • Agency: NIBIB NIH HHS, United States
    Id: T32 EB009383
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM089740
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM117593
  • Agency: NIDA NIH HHS, United States
    Id: K99 DA041500

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Clustal Omega (tool)

RRID:SCR_001591

Software package as multiple sequence alignment tool that uses seeded guide trees and HMM profile-profile techniques to generate alignments between three or more sequences. Accepts nucleic acid or protein sequences in multiple sequence formats NBRF/PIR, EMBL/UniProt, Pearson (FASTA), GDE, ALN/Clustal, GCG/MSF, RSF.

View all literature mentions

Visual Molecular Dynamics (tool)

RRID:SCR_001820

A molecular visualization program for displaying, animating, and analyzing large biomolecular systems using 3-D graphics and built-in scripting. VMD supports computers running MacOS X, Unix, or Windows, is distributed free of charge, and includes source code.

View all literature mentions

Assisted Model Building with Energy Refinement (AMBER) (tool)

RRID:SCR_014230

Software package of molecular simulation programs. It is distributed into AmberTools15 and Amber14. AmberTools15 is a software package which can carry out complete molecular dynamics simulations with either explicit water or generalized Born solvent models. It is distributed in source code format and must be compiled in order to be used. Amber14 builds on AmberTools15 by adding the pmemd program, which provides better performance on multiple CPUs and dramatic speed improvements on GPUs compared to sander (molecular dynamics). GPU info, manuals, and tutorials are available on the website.

View all literature mentions

HEK293 (cell line)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HEK293 (cell line)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions