The intracellular Ca2+ release channel TRPML1 regulates lower urinary tract smooth muscle contractility.

Proceedings of the National Academy of Sciences of the United States of America
Caoimhin S GriffinScott Earley

Abstract

TRPML1 (transient receptor potential mucolipin 1) is a Ca2+-permeable, nonselective cation channel that is predominantly localized to the membranes of late endosomes and lysosomes (LELs). Intracellular release of Ca2+ through TRPML1 is thought to be pivotal for maintenance of intravesicular acidic pH as well as the maturation, fusion, and trafficking of LELs. Interestingly, genetic ablation of TRPML1 in mice (Mcoln1 -/- ) induces a hyperdistended/hypertrophic bladder phenotype. Here, we investigated this phenomenon further by exploring an unconventional role for TRPML1 channels in the regulation of Ca2+-signaling activity and contractility in bladder and urethral smooth muscle cells (SMCs). Four-dimensional (4D) lattice light-sheet live-cell imaging showed that the majority of LELs in freshly isolated bladder SMCs were essentially immobile. Superresolution microscopy revealed distinct nanoscale colocalization of LEL-expressing TRPML1 channels with ryanodine type 2 receptors (RyR2) in bladder SMCs. Spontaneous intracellular release of Ca2+ from the sarcoplasmic reticulum (SR) through RyR2 generates localized elevations of Ca2+ ("Ca2+ sparks") that activate plasmalemmal large-conductance Ca2+-activated K+ (BK) channels, a critica...Continue Reading

References

Dec 1, 1994·Journal of Autonomic Pharmacology·R Chess-WilliamsC Couldwell
Jul 1, 1997·The American Journal of Physiology·T J HeppnerM T Nelson
Jan 14, 1998·Urology·A F Brading
Mar 19, 1999·Experimental Physiology·A F Brading
Feb 9, 2000·American Journal of Physiology. Cell Physiology·J H JaggarM T Nelson
Jul 15, 2000·The Journal of Physiology·G P SergeantN G McHale
Jul 18, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·G M HerreraM T Nelson
Jul 18, 2000·Baillière's Best Practice & Research. Clinical Obstetrics & Gynaecology·D P Keane, S O'Sullivan
Sep 6, 2000·Nature Genetics·R BargalG Bach
Feb 15, 2001·American Journal of Physiology. Cell Physiology·G M HerreraM T Nelson
Feb 1, 2003·Urology·Paul AbramsUNKNOWN Standardisation Sub-Committee of the International Continence Society
Jun 17, 2003·The Journal of Physiology·M A HollywoodK D Thornbury
Aug 13, 2003·The Journal of Urology·Annette SchröderKarl-Erik Andersson
Dec 10, 2003·Urology·Karl Erik Andersson
Mar 17, 2004·The Journal of General Physiology·Guangju JiMichael I Kotlikoff
Jun 9, 2004·The Journal of Biological Chemistry·Andrea L MeredithRichard W Aldrich
Dec 17, 2004·Pharmacological Reviews·Karl-Erik Andersson, Alan J Wein
Feb 25, 2005·Science's STKE : Signal Transduction Knowledge Environment·Craig Montell
Apr 4, 2006·British Journal of Pharmacology·Hikaru HashitaniHikaru Suzuki
Oct 10, 2007·American Journal of Human Genetics·Bhuvarahamurthy VenugopalSusan A Slaugenhaupt
Nov 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·Haoxing XuDavid E Clapham
Dec 7, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Elfaridah P FrazierMartin C Michel
May 21, 2008·Nature Reviews. Neuroscience·Clare J FowlerWilliam C de Groat
Jun 14, 2008·Human Molecular Genetics·Silvia VergarajaureguiRosa Puertollano
Sep 17, 2008·Nature Methods·Jonas FöllingStefan W Hell
Sep 19, 2009·Pflügers Archiv : European journal of physiology·Mohammad A SamieMath P Cuajungco
Jan 16, 2010·FEBS Letters·Xiping ChengHaoxing Xu
Apr 16, 2010·American Journal of Physiology. Renal Physiology·Shaohua ChangSamuel Chacko
Sep 14, 2010·Nano Letters·Jakob BierwagenStefan W Hell
Jun 11, 2011·Neurourology and Urodynamics·Karl-Erik AnderssonClaudius Füllhase
Dec 14, 2011·Nature Reviews. Urology·Georgi V Petkov

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Citations

Dec 3, 2020·Proceedings of the National Academy of Sciences of the United States of America·Gerard P SergeantKeith D Thornbury
Feb 9, 2021·American Journal of Physiology. Renal Physiology·Bernard T DrummGerard P Sergeant

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Methods Mentioned

BETA
fluorescence-activated cell sorting
superresolution microscopy
PCR
FACS
superresolution
confocal microscopy
transgenic

Software Mentioned

ImageJ
pClamp
AcqKnowledge
QuantStudio
IMARIS
Wes

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