scholarly journals Clathrin Isoform CHC22, a Component of Neuromuscular and Myotendinous Junctions, Binds Sorting Nexin 5 and Has Increased Expression during Myogenesis and Muscle Regeneration

2004 ◽  
Vol 15 (7) ◽  
pp. 3181-3195 ◽  
Author(s):  
Mhairi C. Towler ◽  
Paul A. Gleeson ◽  
Sachiko Hoshino ◽  
Paavo Rahkila ◽  
Venus Manalo ◽  
...  
Keyword(s):  
Time Course ◽  
Muscle Development ◽  
Coiled Coil ◽  
Myoblast Differentiation ◽  
Sorting Nexin ◽  
Binding Data ◽  
Differential Binding ◽  
And Function ◽  
Myotendinous Junctions ◽  
Sorting Nexin 5

The muscle isoform of clathrin heavy chain, CHC22, has 85% sequence identity to the ubiquitously expressed CHC17, yet its expression pattern and function appear to be distinct from those of well-characterized clathrin-coated vesicles. In mature muscle CHC22 is preferentially concentrated at neuromuscular and myotendinous junctions, suggesting a role at sarcolemmal contacts with extracellular matrix. During myoblast differentiation, CHC22 expression is increased, initially localized with desmin and nestin and then preferentially segregated to the poles of fused myoblasts. CHC22 expression is also increased in regenerating muscle fibers with the same time course as embryonic myosin, indicating a role in muscle repair. CHC22 binds to sorting nexin 5 through a coiled-coil domain present in both partners, which is absent in CHC17 and coincides with the region on CHC17 that binds the regulatory light-chain subunit. These differential binding data suggest a mechanism for the distinct functions of CHC22 relative to CHC17 in membrane traffic during muscle development, repair, and at neuromuscular and myotendinous junctions.

scholarly journals Novel role of sorting nexin 5 in renal D 1 dopamine receptor trafficking and function: implications for hypertension

2012 ◽  
Vol 27 (5) ◽  
pp. 1808-1819 ◽  
Author(s):  
Van Anthony M. Villar ◽  
Ines Armando ◽  
Hironobu Sanada ◽  
Lauren C. Frazer ◽  
Christen M. Russo ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Receptor Trafficking ◽  
Sorting Nexin ◽  
And Function ◽  
Sorting Nexin 5

scholarly journals Regulated expression and temporal induction of the tail-anchored sarcolemmal-membrane-associated protein is critical for myoblast fusion

2004 ◽  
Vol 381 (3) ◽  
pp. 599-608 ◽  
Author(s):  
Rosa M. GUZZO ◽  
Jeffery WIGLE ◽  
Maysoon SALIH ◽  
Edwin D. MOORE ◽  
Balwant S. TUANA
Keyword(s):  
Muscle Development ◽  
Ectopic Expression ◽  
Coiled Coil ◽  
Myoblast Differentiation ◽  
Sarcolemmal Membrane ◽  
Protein Protein Interaction ◽  
Potent Inhibition ◽  
Regulated Expression ◽  
Associated Proteins

Sarcolemmal-membrane-associated proteins (SLMAPs) define a new class of coiled-coil tail-anchored membrane proteins generated by alternative splicing mechanisms. An in vivo expression analysis indicated that SLMAPs are present in somites (11 days post-coitum) as well as in fusing myotubes and reside at the level of the sarcoplasmic reticulum and transverse tubules in adult skeletal muscles. Skeletal-muscle myoblasts were found to express a single 5.9 kb transcript, which encodes the full-length ∼91 kDa SLMAP3 isoform. Myoblast differentiation was accompanied by the stable expression of the ∼91 kDa SLMAP protein as well as the appearance of an ∼80 kDa isoform. Deregulation of SLMAPs by ectopic expression in myoblasts resulted in a potent inhibition of fusion without affecting the expression of muscle-specific genes. Membrane targeting of the de-regulated SLMAPs was not critical for the inhibition of myotube development. Protein–protein interaction assays indicated that SLMAPs are capable of self-assembling, and the de-regulated expression of mutants that were not capable of forming SLMAP homodimers also inhibited myotube formation. These results imply that regulated levels and the temporal induction of SLMAP isoforms are important for normal muscle development.

scholarly journals Rbm24 Displays Dynamic Functions Required for Myogenic Differentiation During Muscle Regeneration

2020 ◽  
Author(s):  
Raphaëlle Grifone ◽  
Audrey Saquet ◽  
Manon Desgres ◽  
Claudia Sangiorgi ◽  
Caterina Gargano ◽  
...  
Keyword(s):  
Muscle Regeneration ◽  
Muscle Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Myogenic Differentiation ◽  
Regulation Of Gene Expression ◽  
Repair Process ◽  
Myoblast Differentiation ◽  
Adult Mice ◽  
And Function

Abstract Skeletal muscle has a remarkable capacity of regeneration after injury, but the cellular behavior and the regulatory network coordinating different steps of this repair process remain elusive. RNA-binding proteins play key roles in the post-transcriptional regulation of gene expression and are implicated in the maintenance of tissue homeostasis and plasticity. Rbm24 is required for myogenic differentiation during early development, but its function in adult muscle is open for investigation. Here we show that it exerts dynamic functions during muscle regeneration in mice. Consistent with its dynamic subcellular localization during embryonic muscle development, Rbm24 also displays cytoplasm to nucleus translocation during the differentiation of C2C12 myoblasts. In adult mice, Rbm24 mRNA is highly expressed in slow-twitch muscles, and Rbm24 protein is restricted to the myonucleus of myofibers. Upon injury, Rbm24 protein is upregulated in regenerating myofibers and rapidly accumulates in the myonucleus of nascent myofibers. By using satellite cell transplantation, we find that Rbm24 functions sequentially to regulate the differentiation of myofibers and the regeneration of damaged tissues. It is required for myogenin mRNA expression at early stages of muscle injury and for muscle-specific pre-mRNA alternative splicing at late stages of regeneration. These results identify Rbm24 as a multifaceted regulator of myoblast differentiation and function. They also provide insights into the molecular pathway orchestrating the expression of myogenic factors and muscle functional proteins during regeneration.

scholarly journals Roles of the novel coiled-coil protein Rng10 in septum formation during fission yeast cytokinesis

2016 ◽  
Vol 27 (16) ◽  
pp. 2528-2541 ◽  
Author(s):  
Yajun Liu ◽  
I-Ju Lee ◽  
Mingzhai Sun ◽  
Casey A. Lower ◽  
Kurt W. Runge ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Rho Gtpases ◽  
Cellular Localization ◽  
Affinity Purification ◽  
Coiled Coil ◽  
The Novel ◽  
Septum Formation ◽  
Division Site ◽  
And Function

Rho GAPs are important regulators of Rho GTPases, which are involved in various steps of cytokinesis and other processes. However, regulation of Rho-GAP cellular localization and function is not fully understood. Here we report the characterization of a novel coiled-coil protein Rng10 and its relationship with the Rho-GAP Rga7 in fission yeast. Both rng10Δ and rga7Δ result in defective septum and cell lysis during cytokinesis. Rng10 and Rga7 colocalize on the plasma membrane at the cell tips during interphase and at the division site during cell division. Rng10 physically interacts with Rga7 in affinity purification and coimmunoprecipitation. Of interest, Rga7 localization is nearly abolished without Rng10. Moreover, Rng10 and Rga7 work together to regulate the accumulation and dynamics of glucan synthases for successful septum formation in cytokinesis. Our results show that cellular localization and function of the Rho-GAP Rga7 are regulated by a novel protein, Rng10, during cytokinesis in fission yeast.

scholarly journals Acetylcholine Receptors

1972 ◽  
Vol 60 (3) ◽  
pp. 248-262 ◽  
Author(s):  
H. Criss Hartzell ◽  
Douglas M. Fambrough
Keyword(s):  
Acetylcholine Receptors ◽  
Time Course ◽  
Plasma Membranes ◽  
Scintillation Counting ◽  
Receptor Density ◽  
Rat Diaphragm ◽  
Leg Muscles ◽  
And Function ◽  
Quantitative Radioautography ◽  
Ach Receptors

Using 125iodine-labeled α-bungarotoxin (α-BGT-125I) and quantitative radioautography, we have studied the time-course of the change in acetylcholine (ACh) receptor distribution and density occurring in rat diaphragm after denervation. In innervated fibers, ACh receptors are localized at the neuromuscular junction and the extrajunctional receptor density is less than five receptors per square micrometer. The extrajunctional receptor density begins to increase between 2 and 3 days after denervation and increases approximately linearly to 1695 receptors/µm2 at 14 days, subsequently decreasing to 529 receptors/µm2 at 45 days. We have isolated plasma membranes from rat leg muscles at various times after denervation and find that the change in concentration of ACh receptors in the membranes measured by α-BGT-125I binding and scintillation counting follows a time-course similar to the change in ACh receptor density measured radioautographically. Furthermore, we have correlated extrajunctional ACh receptor density measured by radioautography with extrajunctional ACh sensitivity measured by iontophoretic application of ACh and intracellular recording and find that the log of ACh receptor density is related to 0.53 times the log of ACh sensitivity. These results are discussed in terms of the electrophysiological experiments on the ACh receptor and the recent, more biochemical approaches to the study of ACh receptor control and function.

scholarly journals Direct regulation of Arp2/3 complex activity and function by the actin binding protein coronin

2002 ◽  
Vol 159 (6) ◽  
pp. 993-1004 ◽  
Author(s):  
Christine L. Humphries ◽  
Heath I. Balcer ◽  
Jessica L. D'Agostino ◽  
Barbara Winsor ◽  
David G. Drubin ◽  
...  
Keyword(s):  
Binding Protein ◽  
Coiled Coil ◽  
Actin Binding ◽  
Complex Activity ◽  
Actin Binding Protein ◽  
Coiled Coil Domain ◽  
Allele Specific ◽  
And Function

Mechanisms for activating the actin-related protein 2/3 (Arp2/3) complex have been the focus of many recent studies. Here, we identify a novel mode of Arp2/3 complex regulation mediated by the highly conserved actin binding protein coronin. Yeast coronin (Crn1) physically associates with the Arp2/3 complex and inhibits WA- and Abp1-activated actin nucleation in vitro. The inhibition occurs specifically in the absence of preformed actin filaments, suggesting that Crn1 may restrict Arp2/3 complex activity to the sides of filaments. The inhibitory activity of Crn1 resides in its coiled coil domain. Localization of Crn1 to actin patches in vivo and association of Crn1 with the Arp2/3 complex also require its coiled coil domain. Genetic studies provide in vivo evidence for these interactions and activities. Overexpression of CRN1 causes growth arrest and redistribution of Arp2 and Crn1p into aberrant actin loops. These defects are suppressed by deletion of the Crn1 coiled coil domain and by arc35-26, an allele of the p35 subunit of the Arp2/3 complex. Further in vivo evidence that coronin regulates the Arp2/3 complex comes from the observation that crn1 and arp2 mutants display an allele-specific synthetic interaction. This work identifies a new form of regulation of the Arp2/3 complex and an important cellular function for coronin.

scholarly journals Molecular basis for the fold organization and sarcomeric targeting of the muscle atrogin MuRF1

Open Biology ◽  
2014 ◽  
Vol 4 (3) ◽  
pp. 130172 ◽  
Author(s):  
Barbara Franke ◽  
Alexander Gasch ◽  
Dayté Rodriguez ◽  
Mohamed Chami ◽  
Muzamil M. Khan ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Quaternary Structure ◽  
E3 Ubiquitin Ligase ◽  
Coiled Coil ◽  
Trim Protein ◽  
Muscle Catabolism ◽  
And Function ◽  
Helical Region ◽  
Structural Significance

MuRF1 is an E3 ubiquitin ligase central to muscle catabolism. It belongs to the TRIM protein family characterized by a tripartite fold of RING, B-box and coiled-coil (CC) motifs, followed by variable C-terminal domains. The CC motif is hypothesized to be responsible for domain organization in the fold as well as for high-order assembly into functional entities. But data on CC from this family that can clarify the structural significance of this motif are scarce. We have characterized the helical region from MuRF1 and show that, contrary to expectations, its CC domain assembles unproductively, being the B2- and COS-boxes in the fold (respectively flanking the CC) that promote a native quaternary structure. In particular, the C-terminal COS-box seemingly forms an α-hairpin that packs against the CC, influencing its dimerization. This shows that a C-terminal variable domain can be tightly integrated within the conserved TRIM fold to modulate its structure and function. Furthermore, data from transfected muscle show that in MuRF1 the COS-box mediates the in vivo targeting of sarcoskeletal structures and points to the pharmacological relevance of the COS domain for treating MuRF1-mediated muscle atrophy.

scholarly journals Metabolic aspects of the secretion of stored compounds from blood platelets. The effect of NaF at different pH on nucleotide metabolism and function of washed platelets

1981 ◽  
Vol 194 (1) ◽  
pp. 187-192 ◽  
Author(s):  
E H Mürer ◽  
K Davenport ◽  
E Siojo ◽  
H J Day
Keyword(s):  
Time Course ◽  
Adenine Nucleotides ◽  
Blood Platelets ◽  
Fluoride Concentration ◽  
Indirect Evidence ◽  
Inhibitory Effect ◽  
Nucleotide Metabolism ◽  
Wide Range ◽  
And Function ◽  
Special Circumstances

The purpose of this study was to investigate the response of human blood platelets to fluoride at different pH. The results were as follows. (1) Fluoride induced secretion faster and at a lower concentration when pH was lowered. (2) Platelets exposed to 2 mM-fluoride at 0 degrees C at pH 5.3 underwent secretion when first pH and then temperature was raised, although no secretion was seen at 2 mM-fluoride concentration in the absence of the preincubation at low pH. (3) The concentration of [14C]ATP in platelets decreased steeply in response to fluoride before induction of secretion. Addition of antimycin blocked or partly inhibited secretion. Fluoride thus exerts an inhibitory effect on platelet glycolysis before induction of secretion. (4) Fluoride accumulated in the platelet pellet by a time course that preceded secretion. The accumulation was faster and greater at pH 6 than at 7.4. These four points are taken as indirect evidence that fluoride has to penetrate to the interior of the platelet to induce secretion. The activation takes place over a wide range of acid pH in contrast with induction of platelet function via the outside of the plasma membrane. In addition evidence is presented that the salvage pathway may under special circumstances play an important role in the re-synthesis of platelet adenine nucleotides.

A novel natural mutation AαPhe98Ile in the fibrinogen coiled-coil affects fibrinogen function

2014 ◽  
Vol 111 (01) ◽  
pp. 79-87 ◽  
Author(s):  
Zuzana Riedelová-Reicheltová ◽  
Roman Kotlín ◽  
Jiří Suttnar ◽  
Věra Geierová ◽  
Tomáš Riedel ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Coiled Coil ◽  
Fibrin Clot ◽  
Coiled Coil Region ◽  
Platelet Aggregometry ◽  
Sds Page ◽  
Lysis Rate ◽  
Thrombotic Complications ◽  
Natural Mutation ◽  
And Function

SummaryThe aim of this study was to investigate the structure and function of fibrinogen obtained from a patient with normal coagulation times and idiopathic thrombophilia. This was done by SDS-PAGE and DNA sequence analyses, scanning electron microscopy, fibrinopeptide release, fibrin polymerisation initiated by thrombin and reptilase, fibrinolysis, and platelet aggregometry. A novel heterozygous point mutation in the fibrinogen Aα chain, Phe98 to Ile, was found and designated as fibrinogen Vizovice. The mutation, which is located in the RGDF sequence (Aα 95–98) of the fibrinogen coiled-coil region, significantly affected fibrin clot morphology. Namely, the clot formed by fibrinogen Vizovice contained thinner and curled fibrin fibers with reduced length. Lysis of the clots prepared from Vizovice plasma and isolated fibrinogen were found to be impaired. The lysis rate of Vizovice clots was almost four times slower than the lysis rate of control clots. In the presence of platelets agonists the mutant fibrinogen caused increased platelet aggregation. The data obtained show that natural mutation of Phe98 to Ile in the fibrinogen Aα chain influences lateral aggregation of fibrin protofibrils, fibrinolysis, and platelet aggregation. They also suggest that delayed fibrinolysis, together with the abnormal fibrin network morphology and increased platelet aggregation, may be the direct cause of thrombotic complications in the patient associated with pregnancy loss.

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