Regulation of TRPC1 and TRPC4 Cation Channels Requires an α1-Syntrophin-dependent Complex in Skeletal Mouse Myotubes*

The dystrophin-associated protein complex (DAPC) is essential for skeletal muscle, and the lack of dystrophin in Duchenne muscular dystrophy results in a reduction of DAPC components such as syntrophins and in fiber necrosis. By anchoring various molecules, the syntrophins may confer a role in cell signaling to the DAPC. Calcium disorders and abnormally elevated cation influx in dystrophic muscle cells have suggested that the DAPC regulates some sarcolemmal cationic channels. We demonstrated previously that mini-dystrophin and α1-syntrophin restore normal cation entry in dystrophin-deficient myotubes and that sarcolemmal TRPC1 channels associate with dystrophin and the bound PDZ domain of α1-syntrophin. This study shows that small interfering RNA (siRNA) silencing of α1-syntrophin dysregulated cation influx in myotubes. Moreover, deletion of the PDZ-containing domain prevented restoration of normal cation entry by α1-syntrophin transfection in dystrophin-deficient myotubes. TRPC1 and TRPC4 channels are expressed at the sarcolemma of muscle cells; forced expression or siRNA silencing showed that cation influx regulated by α1-syntrophin is supported by TRPC1 and TRPC4. A molecular association was found between TRPC1 and TRPC4 channels and the α1-syntrophin-dystrophin complex. TRPC1 and TRPC4 channels may form sarcolemmal channels anchored to the DAPC, and α1-syntrophin is necessary to maintain the normal regulation of TRPC-supported cation entry in skeletal muscle. Cation channels with DAPC form a signaling complex that modulates cation entry and may be crucial for normal calcium homeostasis in skeletal muscles.

• Publication year

  2009

• Venue

  Journal of Biological Chemistry

• Publication date

  2009-10-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M109.012872PMID 19812031PMCID PMC2794741
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Skeletal myoblasts overexpressing relaxin improve differentiation and communication of primary murine cardiomyocyte cell cultures.

  2009cited by this paper
• TRPC1 binds to caveolin-3 and is regulated by Src kinase – role in Duchenne muscular dystrophy

  2008cited by this paper
• Mice Lacking Homer 1 Exhibit a Skeletal Myopathy Characterized by Abnormal Transient Receptor Potential Channel Activity

  2008cited by this paper
• Functional Requirement for Orai1 in Store-operated TRPC1-STIM1 Channels*

  2008cited by this paper
• Regulation of the cellular localization and function of human transient receptor potential channel 1 by other members of the TRPC family.

  2008cited by this paper
• Store-operated Ca2+ entry in platelets occurs independently of transient receptor potential (TRP) C1

  2008cited by this paper
• Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release–activated calcium channels

  2008cited by this paper
• Differential dependence of store‐operated and excitation‐coupled Ca2+ entry in skeletal muscle on STIM1 and Orai1

  2008cited by this paper
• Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels

  2008cited by this paper
• STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle

  2008cited by this paper
• Some assembly required: constructing the elementary units of store-operated Ca2+ entry.

  2007cited by this paper
• TRPC1: a core component of store-operated calcium channels.

  2007cited by this paper
• Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(−/−) mice

  2007cited by this paper
• Calcium misregulation and the pathogenesis of muscular dystrophy.

  2007cited by this paper
• Revisiting TRPC1 and TRPC6 mechanosensitivity

  2007cited by this paper
• Regulation of capacitative calcium entries by α1‐syntrophin: association of TRPC1 with dystrophin complex and the PDZ domain of α1‐syntrophin

  2007cited by this paper
• Regulation of capacitative calcium entries by alpha1-syntrophin: association of TRPC1 with dystrophin complex and the PDZ domain of alpha1-syntrophin.

  2007cited by this paper
• STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels

  2007cited by this paper
• Orai proteins interact with TRPC channels and confer responsiveness to store depletion

  2007cited by this paper
• Store‐operated Ca2+ entry during intracellular Ca2+ release in mammalian skeletal muscle

  2007cited by this paper
• Functional role of store‐operated and stretch‐activated channels in murine adult skeletal muscle fibres

  2006cited by this paper
• A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function

  2006cited by this paper
• Ca2+-independent phospholipase A2 enhances store-operated Ca2+ entry in dystrophic skeletal muscle fibers

  2006cited by this paper
• Regulation of store‐operated calcium entries and mitochondrial uptake by minidystrophin expression in cultured myotubes

  2006cited by this paper
• STIM1 carboxyl-terminus activates native SOC, Icrac and TRPC1 channels

  2006cited by this paper
• TRPC1: store-operated channel and more

  2005cited by this paper
• The Syntrophin-Dystrobrevin Subcomplex in Human Neuromuscular Disorders

  2005cited by this paper
• TRPC1 forms the stretch-activated cation channel in vertebrate cells

  2005cited by this paper
• TRPC5 activation kinetics are modulated by the scaffolding protein ezrin/radixin/moesin‐binding phosphoprotein‐50 (EBP50)

  2004cited by this paper
• Mini‐dystrophin restores L‐type calcium currents in skeletal muscle of transgenic mdx mice

  2004cited by this paper
• The Potassium Channel Kir4.1 Associates with the Dystrophin-Glycoprotein Complex via α-Syntrophin in Glia*

  2004cited by this paper
• Syntrophin gamma 2 regulates SCN5A gating by a PDZ domain-mediated interaction.

  2003cited by this paper
• Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors.

  2003cited by this paper
• Syntrophin γ2 Regulates SCN5A Gating by a PDZ Domain-mediated Interaction*

  2003cited by this paper
• Changes in mechanosensitive channel gating following mechanical stimulation in skeletal muscle myotubes from the mdx mouse

  2002cited by this paper
• Subunit composition of mammalian transient receptor potential channels in living cells

  2002cited by this paper
• The PDZ-interacting domain of TRPC4 controls its localization and surface expression in HEK293 cells.

  2002cited by this paper
• Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx) mouse skeletal muscle fibers

  2002cited by this paper
• Structural domains required for channel function of the mouse transient receptor potential protein homologue TRP1β

  2002cited by this paper
• Selective Association of TRPC Channel Subunits in Rat Brain Synaptosomes* 210

  2002cited by this paper
• Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4−/− mice

  2001cited by this paper
• Depletion of Ca2+ in the sarcoplasmic reticulum stimulates Ca2+ entry into mouse skeletal muscle fibres

  2001cited by this paper
• Calcium currents and transients in co‐cultured contracting normal and Duchenne muscular dystrophy human myotubes

  2001cited by this paper
• TRPC1 and TRPC5 form a novel cation channel in mammalian brain.

  2001cited by this paper
• Cationic channels in normal and dystrophic human myotubes.

  2001cited by this paper
• Association of Mammalian Trp4 and Phospholipase C Isozymes with a PDZ Domain-containing Protein, NHERF*

  2000cited by this paper
• Assembly of Trp1 in a Signaling Complex Associated with Caveolin-Scaffolding Lipid Raft Domains*

  2000cited by this paper
• Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins

  1998cited by this paper
• Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle.

  1998cited by this paper
• Differential Association of Syntrophin Pairs with the Dystrophin Complex

  1997cited by this paper
• Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy.

  1996cited by this paper
• A mammalian capacitative calcium entry channel homologous to Drosophila TRP and TRPL.

  1996cited by this paper
• Cloning and functional expression of a human Ca2+-permeable cation channel activated by calcium store depletion.

  1996cited by this paper
• A Capacitative Calcium Current in Cultured Skeletal Muscle Cells Is Mediated by the Calcium-specific Leak Channel and Inhibited by Dihydropyridine Compounds*

  1996cited by this paper
• Hypoosmotic shocks induce elevation of resting calcium level in Duchenne muscular dystrophy myotubes contracting in vitro.

  1996cited by this paper
• Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy.

  1995cited by this paper
• Mechanosensitive ion channels in skeletal muscle from normal and dystrophic mice.

  1994cited by this paper
• Two forms of mouse syntrophin, a 58 kd dystrophin-associated protein, differ in primary structure and tissue distribution.

  1993cited by this paper
• Membrane organization of the dystrophin-glycoprotein complex.

  1991cited by this paper
• Stretch‐sensitive channels in developing muscle cells from a mouse cell line.

  1990cited by this paper
• Calcium currents in normal and dystrophic human skeletal muscle cells in culture.

  1990cited by this paper
• Different types of Ca2+ channels in mammalian skeletal muscle cells in culture.

  1986cited by this paper

• Effects of aging on calcium channels in skeletal muscle

  2025cites this paper
• Transient Receptor Potential channels (TRP) in GtoPdb v.2025.4

  2025cites this paper
• Ion channels as biomarkers of altered myogenesis in myofiber precursors of Duchenne muscular dystrophy

  2024influential citation
• TRPC1: The housekeeper of the hippocampus.

  2024cites this paper
• Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy

  2023influential citation
• Transient Receptor Potential channels (TRP) in GtoPdb v.2023.2

  2023cites this paper
• Transient Receptor Potential channels (TRP) in GtoPdb v.2023.1

  2023cites this paper
• Synaptic alterations as a neurodevelopmental trait of Duchenne muscular dystrophy.

  2022cites this paper
• The SOCE Machinery: An Unbalanced Knowledge between Left and Right Ventricular Pathophysiology

  2022cites this paper
• Evaluation of the dystrophin carboxy-terminal domain for micro-dystrophin gene therapy in cardiac and skeletal muscles in the DMDmdx rat model

  2022cites this paper
• Transient Receptor Potential channels (TRP) in GtoPdb v.2022.1

  2022cites this paper
• Distribution and Assembly of TRP Ion Channels.

  2021cites this paper
• Complexity of skeletal muscle degeneration: multi-systems pathophysiology and organ crosstalk in dystrophinopathy

  2021cites this paper
• Role of Store-Operated Ca2+ Entry in the Pulmonary Vascular Remodeling Occurring in Pulmonary Arterial Hypertension

  2021cites this paper
• α‐Syntrophin alleviates ER stress to maintain protein homeostasis during myoblast differentiation

  2021cites this paper
• The Dystrophin Node as Integrator of Cytoskeletal Organization, Lateral Force Transmission, Fiber Stability and Cellular Signaling in Skeletal Muscle

  2021cites this paper
• Abnormal Calcium Handling in Duchenne Muscular Dystrophy: Mechanisms and Potential Therapies

  2021cites this paper
• TRPCs: Influential Mediators in Skeletal Muscle

  2020cites this paper
• Calcium Channels in Adult Brain Neural Stem Cells and in Glioblastoma Stem Cells

  2020cites this paper
• Fine Tuning of Calcium Constitutive Entry by Optogenetically-Controlled Membrane Polarization: Impact on Cell Migration

  2020cites this paper
• Specific Upregulation of TRPC1 and TRPC5 Channels by Mineralocorticoid Pathway in Adult Rat Ventricular Cardiomyocytes

  2019cites this paper
• ABC of multifaceted dystrophin glycoprotein complex (DGC)

  2018cites this paper
• Syntrophins entangled in cytoskeletal meshwork: Helping to hold it all together

  2018cites this paper
• Deregulation of calcium homeostasis in Bcr-Abl-dependent chronic myeloid leukemia

  2018cites this paper
• Biochemical and Functional Interplay Between Ion Channels and the Components of the Dystrophin-Associated Glycoprotein Complex

  2018cites this paper
• The Complex Role of Store Operated Calcium Entry Pathways and Related Proteins in the Function of Cardiac, Skeletal and Vascular Smooth Muscle Cells

  2018cites this paper
• TRP Ion Channels: From Distribution to Assembly

  2018cites this paper
• Biological Role of TRPC1 in Myogenesis, Regeneration, and Disease

  2017cites this paper
• STIM-TRP Pathways and Microdomain Organization: Contribution of TRPC1 in Store-Operated Ca2+ Entry: Impact on Ca2+ Signaling and Cell Function.

  2017cites this paper
• α‐Syntrophin stabilizes catalase to reduce endogenous reactive oxygen species levels during myoblast differentiation

  2017cites this paper
• Calcium Channels in Vascular Smooth Muscle.

  2017cites this paper
• A focus on extracellular Ca2+ entry into skeletal muscle

  2017cites this paper
• Neurological and Motor Disorders: TRPC in the Skeletal Muscle.

  2017cites this paper
• TRPC1 and TRPC4 channels functionally interact with STIM1L to promote myogenesis and maintain fast repetitive Ca2+ release in human myotubes.

  2017cites this paper
• Mechanical Regulation of Striated Muscle Nitric Oxide Signaling in Muscular Dystrophy

  2017cites this paper
• Role of TRPC Channels in Store-Operated Calcium Entry.

  2016cites this paper
• Role of Scaffolding Proteins in the Regulation of TRPC-Dependent Calcium Entry.

  2016cites this paper
• The involvement of transient receptor potential canonical type 1 in skeletal muscle regrowth after unloading‐induced atrophy

  2016cites this paper
• Analysis of the dystrophin interactome

  2016cites this paper
• Rôle de la signalisation calcique dans la leucémie myéloïde chronique

  2016cites this paper
• Absence of Dystrophin Disrupts Skeletal Muscle Signaling: Roles of Ca2+, Reactive Oxygen Species, and Nitric Oxide in the Development of Muscular Dystrophy.

  2016cites this paper
• Axial stretch-dependent cation entry in dystrophic cardiomyopathy: Involvement of several TRPs channels.

  2016cites this paper
• α-Syntrophin is involved in the survival signaling pathway in myoblasts under menadione-induced oxidative stress.

  2016cites this paper
• Store-operated calcium entry: unveiling the calcium handling signalplex.

  2015influential citation
• Classical Transient Receptor Potential 1 (TRPC1): Channel or Channel Regulator?

  2014cites this paper
• Dystrophin complex functions as a scaffold for signalling proteins.

  2014cites this paper
• TRPC4- and TRPC4-containing channels.

  2014cites this paper
• Gestational Diabetes Is Characterized by Reduced Mitochondrial Protein Expression and Altered Calcium Signaling Proteins in Skeletal Muscle

  2014cites this paper
• Physiological functions and regulation of TRPC channels.

  2014cites this paper
• Inositol 1,4,5 trisphosphate receptor 1 is a key player of human myoblast differentiation.

  2014cites this paper
• During post-natal human myogenesis, normal myotube size requires TRPC1- and TRPC4-mediated Ca2+ entry

  2013cites this paper
• Cardiac and Respiratory Dysfunction in Duchenne Muscular Dystrophy and the Role of Second Messengers

  2013cites this paper
• Caveolae Regulation of Mechanosensitive Channel Function in Myotubes

  2013cites this paper
• Involvement of TRPV2 and SOCE in calcium influx disorder in DMD primary human myotubes with a specific contribution of α1-syntrophin and PLC/PKC in SOCE regulation.

  2013cites this paper
• Sarco (Endo) Plasmic Reticulum Calcium Atpases (SERCA) Isoforms in the Normal and Diseased Cardiac, Vascular and Skeletal Muscle

  2013cites this paper
• Dystrophin deficiency leads to disturbance of LAMP1-vesicle-associated protein secretion

  2013cites this paper
• Evolution of mechanisms of Ca2+-signalization. Role of Ca2+ in regulation of specialized cell functions

  2013cites this paper
• Expression and localization of TRPC proteins in rat ventricular myocytes at various developmental stages

  2013cites this paper
• Calcium Signaling at the Blood–Brain Barrier in Stroke

  2012cites this paper
• A new model for the dystrophin associated protein complex in striated muscles

  2012cites this paper
• Dystrophin/α1-syntrophin scaffold regulated PLC/PKC-dependent store-operated calcium entry in myotubes.

  2012cites this paper
• Chapter 56 – Control of Resting Ca2+ Concentration in Skeletal Muscle

  2012cites this paper
• Rôle des entrées capacitives et de TRPV2 dans la dérégulation de l'homéostasie calcique dans le muscle squelettique humain : implication dans la dystrophie musculaire de Duchenne

  2012influential citation
• TRP channels in normal and dystrophic skeletal muscle.

  2012cites this paper
• Orai and TRP channels in skeletal muscle cells

  2012influential citation
• Activation of Transient Receptor Potential Canonical 3 (TRPC3)-mediated Ca2+ Entry by A1 Adenosine Receptor in Cardiomyocytes Disturbs Atrioventricular Conduction*

  2012cites this paper
• entry by A1 adenosine receptor in cardiomyocytes disturbs atrio-ventricular conduction

  2012cites this paper
• Expression and association of TRPC1 with TRPC3 during skeletal myogenesis

  2011cites this paper
• STIM1 as a key regulator for Ca2+ homeostasis in skeletal-muscle development and function

  2011cites this paper
• LQTS-associated mutation A257G in α1-syntrophin interacts with the intragenic variant P74L to modify its biophysical phenotype.

  2011cites this paper
• Duchenne muscular dystrophy--what causes the increased membrane permeability in skeletal muscle?

  2011cites this paper
• TRP channels in skeletal muscle: gene expression, function and implications for disease.

  2011cites this paper
• Blockade of TNF in vivo using cV1q antibody reduces contractile dysfunction of skeletal muscle in response to eccentric exercise in dystrophic mdx and normal mice.

  2011cites this paper
• Stretch-activated calcium channel protein TRPC1 is correlated with the different degrees of the dystrophic phenotype in mdx mice.

  2011cites this paper
• The Role of Alpha-Dystrobrevin in Striated Muscle

  2011cites this paper
• Hyperthermic seizures and aberrant cellular homeostasis in Drosophila dystrophic muscles

  2011cites this paper
• Exercise and muscular dystrophy: implications and analysis of effects on musculoskeletal and cardiovascular systems.

  2011cites this paper
• Stress and muscular dystrophy: a genetic screen for dystroglycan and dystrophin interactors in Drosophila identifies cellular stress response components.

  2011cites this paper
• TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts

  2010influential citation
• TRPC1: Subcellular Localization?

  2010cites this paper
• Therapeutic interventions for Duchenne Muscular Dystrophy - studies in the mdx mouse

  2010cites this paper
• Ca2+ channels and skeletal muscle diseases.

  2010cites this paper
• uchenne muscular dystrophy – What causes the increased membrane ermeability in skeletal muscle ?

  2010cites this paper
• Regulation by scaffolding proteins of canonical transient receptor potential channels in striated muscle

  2009cites this paper