Muscles of mice deficient in α-sarcoglycan maintain large masses and near control force values throughout the life span

α-Sarcoglycan-deficient ( Sgca-null) mice provide potential for elucidating the pathogenesis of limb girdle muscular dystrophy type 2D (LGMD 2D) as well as for studying the effectiveness of therapeutic strategies. Skeletal muscles of Sgca-null mice demonstrate an early onset of extensive fiber necrosis, degeneration, and regeneration, but the progression of the pathology and the effects on muscle structure and function throughout the life span are not known. Thus the phenotypic accuracy of the Sgca-null mouse as a model of LGMD 2D has not been fully established. To investigate skeletal muscle structure and function in the absence of α-sarcoglycan throughout the life span, we analyzed extensor digitorum longus and soleus muscles of male and female Sgca-null and wild-type mice at 3, 6, 12, and 18 mo of age. Maximum isometric forces and powers were measured in vitro at 25°C. Also determined were individual myofiber cross-sectional areas and numbers, water content, and the proportion of the cross section occupied by connective tissue. Muscle masses were 40–100% larger for Sgca-null compared with age- and gender-matched wild-type mice, with the majority of the increased muscle mass for Sgca-null mice attributable to greater connective tissue and water contents. Although the greater mass of muscles in Sgca-null mice was primarily noncontractile material, absolute forces and powers were maintained near control levels at all ages, indicating a successful adaptation to the deficiency in α-sarcoglycan not observed at any age in LGMD 2D patients.

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Lower leg muscle structure and function are altered in long-distance runners with medial tibial stress syndrome: a case control study

Journal of Foot and Ankle Research ◽

10.1186/s13047-021-00485-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Joshua Mattock ◽

Julie R. Steele ◽

Karen J. Mickle

Keyword(s):

Lower Leg ◽

Structure And Function ◽

Flexor Hallucis Longus ◽

Plantar Flexor ◽

Distance Runners ◽

Long Distance ◽

Cross Sectional ◽

Muscle Structure ◽

Leg Muscle ◽

And Function

Abstract Background Medial tibial stress syndrome (MTSS) is a common lower leg injury experienced by runners. Although numerous risk factors are reported in the literature, many are non-modifiable and management of the injury remains difficult. Lower leg muscle structure and function are modifiable characteristics that influence tibial loading during foot-ground contact. Therefore, this study aimed to determine whether long-distance runners with MTSS displayed differences in in vivo lower leg muscle structure and function than matched asymptomatic runners. Methods Lower leg structure was assessed using ultrasound and a measure of lower leg circumference to quantify muscle cross-sectional area, thickness and lean lower leg girth. Lower leg function was assessed using a hand-held dynamometer to quantify maximal voluntary isometric contraction strength and a single leg heel raise protocol was used to measure ankle plantar flexor endurance. Outcome variables were compared between the limbs of long-distance runners suffering MTSS (n = 20) and matched asymptomatic controls (n = 20). Means, standard deviations, 95 % confidence intervals, mean differences and Cohen’s d values were calculated for each variable for the MTSS symptomatic and control limbs. Results MTSS symptomatic limbs displayed a significantly smaller flexor hallucis longus cross-sectional area, a smaller soleus thickness but a larger lateral gastrocnemius thickness than the control limbs. However, there was no statistical difference in lean lower leg girth. Compared to the matched control limbs, MTSS symptomatic limbs displayed deficits in maximal voluntary isometric contraction strength of the flexor hallucis longus, soleus, tibialis anterior and peroneal muscles, and reduced ankle plantar flexor endurance capacity. Conclusions Differences in lower leg muscle structure and function likely render MTSS symptomatic individuals less able to withstand the negative tibial bending moment generated during midstance, potentially contributing to the development of MTSS. The clinical implications of these findings suggest that rehabilitation protocols for MTSS symptomatic individuals should aim to improve strength of the flexor hallucis longus, soleus, tibialis anterior and peroneal muscles along with ankle plantar flexor endurance. However, the cross-sectional study design prevents us determining whether between group differences were a cause or effect of MTSS. Therefore, future prospective studies are required to substantiate the study findings.

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A Non-Tumor Suppressor Role for Basal p19ARF in Maintaining Nucleolar Structure and Function

Molecular and Cellular Biology ◽

10.1128/mcb.00484-07 ◽

2007 ◽

Vol 28 (3) ◽

pp. 1068-1080 ◽

Cited By ~ 32

Author(s):

Anthony J. Apicelli ◽

Leonard B. Maggi ◽

Angela C. Hirbe ◽

Alexander P. Miceli ◽

Mary E. Olanich ◽

...

Keyword(s):

Nuclear Export ◽

Ribosome Biogenesis ◽

Physiological Function ◽

Structure And Function ◽

Wild Type ◽

Nucleolar Structure ◽

Wild Type Mefs ◽

And Function

ABSTRACT The nucleolus is the center of ribosome synthesis, with the nucleophosmin (NPM) and p19ARF proteins antagonizing one another to either promote or inhibit growth. However, basal NPM and ARF proteins form nucleolar complexes whose functions remain unknown. Nucleoli from Arf −/ − cells displayed increased nucleolar area, suggesting that basal ARF might regulate key nucleolar functions. Concordantly, ribosome biogenesis and protein synthesis were dramatically elevated in the absence of Arf, causing these cells to exhibit tremendous gains in protein amounts and increases in cell volume. The transcription of ribosomal DNA (rDNA), the processing of nascent rRNA molecules, and the nuclear export of ribosomes were all increased in the absence of ARF. Similar results were obtained using targeted lentiviral RNA interference of ARF in wild-type MEFs. Postmitotic osteoclasts from Arf-null mice exhibited hyperactivity in vitro and in vivo, demonstrating a physiological function for basal ARF. Moreover, the knockdown of NPM blocked the increases in Arf −/− ribosome output and osteoclast activity, demonstrating that these gains require NPM. Thus, basal ARF proteins act as a monitor of steady-state ribosome biogenesis and growth independent of their ability to prevent unwarranted hyperproliferation.

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Biomimetic sponges improve muscle structure and function following volumetric muscle loss

10.1101/2020.05.20.106823 ◽

2020 ◽

Author(s):

Gabriel Haas ◽

Andrew Dunn ◽

Josh Madsen ◽

Peter Genovese ◽

Andrew Lin ◽

...

Keyword(s):

Significant Loss ◽

Structure And Function ◽

Muscle Loss ◽

Cross Sectional ◽

Fk 506 ◽

Traumatic Injuries ◽

Muscle Structure ◽

Volumetric Muscle Loss ◽

Isometric Torque ◽

And Function

AbstractSkeletal muscle is inept in regenerating after traumatic injuries such as volumetric muscle loss (VML) due to significant loss of basal lamina and the resident satellite cells. Currently, there are no approved therapies for the treatment of muscle tissue following trauma. In this study, biomimetic sponges composed of gelatin, collagen, laminin-111, and FK-506 were used for the treatment of VML in a rodent model. We observed that biomimetic sponge treatment improved muscle structure and function while modulating inflammation and limiting the extent of fibrotic tissue deposition. Specifically, sponge treatment increased the total number of myofibers, type 2B fiber cross-sectional area, myosin: collagen ratio, myofibers with central nuclei, and peak isometric torque compared to untreated VML injured muscles. As an acellular scaffold, biomimetic sponges provide a promising “off-the-shelf” clinical therapy for VML.

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Conserved Residues in the C-Terminal Domain Affect the Structure and Function of CYP38 in Arabidopsis

Frontiers in Plant Science ◽

10.3389/fpls.2021.630644 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lujing Shi ◽

Lele Du ◽

Jingru Wen ◽

Xiumei Zong ◽

Wene Zhao ◽

...

Keyword(s):

Thylakoid Membrane ◽

Structure And Function ◽

Wild Type ◽

Yeast Two Hybrid ◽

Conserved Residues ◽

Terminal Domain ◽

Target Binding ◽

And Function ◽

Two Hybrid

Arabidopsis cyclophilin38 (CYP38) is a thylakoid lumen protein critial for PSII assembly and maintenance, and its C-terminal region serves as the target binding domain. We hypothesized that four conserved residues (R290, F294, Q372, and F374) in the C-terminal domain are critical for the structure and function of CYP38. In yeast two-hybrid and protein pull-down assays, CYP38s with single-sited mutations (R290A, F294A, Q372A, or F374A) did not interact with the CP47 E-loop as the wild-type CYP38. In contrast, CYP38 with the R290A/F294A/Q372A/F374A quadruple mutation could bind the CP47 E-loop. Gene transformation analysis showed that the quadruple mutation prevented CYP38 to efficiently complement the mutant phenotype of cyp38. The C-terminal domain half protein with the quadruple mutation, like the wild-type one, could interact with the N-terminal domain or the CP47 E-loop in vitro. The cyp38 plants expressing CYP38 with the quadruple mutation showed a similar BN-PAGE profile as cyp38, but distinct from the wild type. The CYP38 protein with the quadruple mutation associated with the thylakoid membrane less efficiently than the wild-type CYP38. We concluded that these four conserved residues are indispensable as changes of all these residues together resulted in a subtle conformational change of CYP38 and reduced its intramolecular N-C interaction and the ability to associate with the thylakoid membrane, thus impairing its function in chloroplast.

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The skeletal muscle circadian clock regulates sarcomere length homeostasis through titin splicing

10.1101/2021.05.27.445953 ◽

2021 ◽

Author(s):

Lance Riley ◽

Xiping Zhang ◽

Joseph Mijares ◽

David Hammers ◽

Hailey Olafson ◽

...

Keyword(s):

Skeletal Muscle ◽

Molecular Clock ◽

Sarcomere Length ◽

Structure And Function ◽

Sarcomeric Proteins ◽

Muscle Structure ◽

Splicing Regulator ◽

And Function ◽

Ig Domain

Circadian rhythms in skeletal muscle are maintained by a transcriptional-translational feedback loop known as the molecular clock. While previous research suggested a role for the molecular clock in regulating skeletal muscle structure and function, no mechanisms have connected the molecular clock to sarcomeric proteins. Utilizing inducible, skeletal muscle specific, Bmal1 knockout (iMSBmal1-/-) mice, we show that deletion of the skeletal muscle molecular clock alters titin isoform and skeletal muscle sarcomere length. We then use U7 snRNPs in myotubes to directly alter titin splicing in vitro. Truncating the titin proximal Ig domain results in altered sarcomere length. Finally, we identify a mechanism whereby the skeletal muscle molecular clock regulates titin isoform expression through RBM20, a potent splicing regulator of the titin transcript. Our findings demonstrate the importance of the skeletal muscle molecular clock in maintaining sarcomere length homogeneity through its regulation of RBM20 expression. Because circadian rhythm disruption is a feature of many diseases, our results highlight a pathway that could be targeted to maintain skeletal muscle structure and function in a range of pathologies.

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A VISIBLE ALLELE OF THE MUSCLE GENE sup-10 X OF C. ELEGANS

Genetics ◽

10.1093/genetics/113.1.63 ◽

1986 ◽

Vol 113 (1) ◽

pp. 63-72

Author(s):

Iva Greenwald ◽

H Robert Horvitz

Keyword(s):

Caenorhabditis Elegans ◽

Protein Complex ◽

Structure And Function ◽

The Other ◽

Wild Type ◽

C Elegans ◽

Muscle Structure ◽

New Gene ◽

Muscle Gene ◽

And Function

ABSTRACT In this paper, we extend our previous analyses of a set of genes in Caenorhabditis elegans that are involved in muscle structure and function: unc-93 III, sup-9 II, sup-10 X and sup-11 I. We describe an unusual, visible allele of sup-10, examine how this allele interacts genetically with mutations in other genes of this set and propose that the wild-type products of the unc-93 and sup-10 loci may be components of a protein complex. We also describe a new gene of this set, sup-18 III, and the interaction of sup-18 alleles with mutations in the other genes.

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