scholarly journals Drosophila Nesprin-1 Isoforms Differentially Contribute to Muscle Function

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3061
Author(s):  
Alexandre Rey ◽  
Laurent Schaeffer ◽  
Bénédicte Durand ◽  
Véronique Morel
Keyword(s):  
Muscular Dystrophy ◽  
Subcellular Localization ◽  
Actin Cytoskeleton ◽  
Muscle Function ◽  
Scaffold Protein ◽  
Global Function ◽  
Calponin Homology ◽  
Drosophila Larvae ◽  
Large Scaffold

Nesprin-1 is a large scaffold protein connecting nuclei to the actin cytoskeleton via its KASH and Calponin Homology domains, respectively. Nesprin-1 disconnection from nuclei results in altered muscle function and myonuclei mispositioning. Furthermore, Nesprin-1 mutations are associated with muscular pathologies such as Emery Dreifuss muscular dystrophy and arthrogryposis. Nesprin-1 was thus proposed to mainly contribute to muscle function by controlling nuclei position. However, Nesprin-1′s localisation at sarcomere’s Z-discs, its involvement in organelles’ subcellular localization, as well as the description of numerous isoforms presenting different combinations of Calponin Homology (CH) and KASH domains, suggest that the contribution of Nesprin-1 to muscle functions is more complex. Here, we investigate the roles of Nesprin-1/Msp300 isoforms in muscle function and subcellular organisation using Drosophila larvae as a model. Subsets of Msp300 isoform were down-regulated by muscle-specific RNAi expression and muscle global function and morphology were assessed. We show that nuclei anchoring in mature muscle and global muscle function are disconnected functions associated with different Msp300 isoforms. Our work further uncovers a new and unsuspected role of Msp300 in myofibril registration and nuclei peripheral displacement supported by Msp300 CH containing isoforms, a function performed by Desmin in mammals.

scholarly journals DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies

2020 ◽  
Vol 29 (17) ◽  
pp. 2855-2871
Author(s):  
Andrea L Reid ◽  
Yimin Wang ◽  
Adrienne Samani ◽  
Rylie M Hightower ◽  
Michael A Lopez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Function ◽  
Myogenic Differentiation ◽  
Nucleotide Exchange ◽  
Dystrophic Muscle ◽  
Guanine Nucleotide Exchange ◽  
Myogenic Factors

Abstract DOCK3 is a member of the DOCK family of guanine nucleotide exchange factors that regulate cell migration, fusion and viability. Previously, we identified a dysregulated miR-486/DOCK3 signaling cascade in dystrophin-deficient muscle, which resulted in the overexpression of DOCK3; however, little is known about the role of DOCK3 in muscle. Here, we characterize the functional role of DOCK3 in normal and dystrophic skeletal muscle. Utilizing Dock3 global knockout (Dock3 KO) mice, we found that the haploinsufficiency of Dock3 in Duchenne muscular dystrophy mice improved dystrophic muscle pathologies; however, complete loss of Dock3 worsened muscle function. Adult Dock3 KO mice have impaired muscle function and Dock3 KO myoblasts are defective for myogenic differentiation. Transcriptomic analyses of Dock3 KO muscles reveal a decrease in myogenic factors and pathways involved in muscle differentiation. These studies identify DOCK3 as a novel modulator of muscle health and may yield therapeutic targets for treating dystrophic muscle symptoms.

scholarly journals Netrin instructs synaptic vesicle clustering through Rac GTPase, MIG-10, and the actin cytoskeleton

2012 ◽  
Vol 197 (1) ◽  
pp. 75-88 ◽  
Author(s):  
Andrea K.H. Stavoe ◽  
Daniel A. Colón-Ramos
Keyword(s):  
Cell Migration ◽  
Subcellular Localization ◽  
Actin Cytoskeleton ◽  
Axon Guidance ◽  
Synaptic Vesicle ◽  
Active Zone ◽  
Rac Gtpase ◽  
Signaling Modules

Netrin is a chemotrophic factor known to regulate a number of neurodevelopmental processes, including cell migration, axon guidance, and synaptogenesis. Although the role of Netrin in synaptogenesis is conserved throughout evolution, the mechanisms by which it instructs synapse assembly are not understood. Here we identify a mechanism by which the Netrin receptor UNC-40/DCC instructs synaptic vesicle clustering in vivo. UNC-40 localized to presynaptic regions in response to Netrin. We show that UNC-40 interacted with CED-5/DOCK180 and instructed CED-5 presynaptic localization. CED-5 in turn signaled through CED-10/Rac1 and MIG-10/Lamellipodin to organize the actin cytoskeleton in presynaptic regions. Localization of this signaling pathway to presynaptic regions was necessary for synaptic vesicle clustering during synapse assembly but not for the subcellular localization of active zone proteins. Thus, vesicle clustering and localization of active zone proteins are instructed by separate pathways downstream of Netrin. Our data indicate that signaling modules known to organize the actin cytoskeleton during guidance can be co-opted to instruct synaptic vesicle clustering.

scholarly journals Role of hypoxia in muscle function and muscular dystrophy

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Matias M Mosqueira ◽  
Santosh M Baby ◽  
Murat Budak ◽  
Sasha Bogdanovich ◽  
Gabriel Willmann ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Muscle Function

Have Duchenne Muscular Dystrophy Patients an Increased Cancer Risk?

2021 ◽  
pp. 1-5
Author(s):  
Gian Luca Vita ◽  
Luisa Politano ◽  
Angela Berardinelli ◽  
Giuseppe Vita
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Systematic Investigation ◽  
Mdx Mice ◽  
True Incidence ◽  
Patients With Cancer ◽  
Dmd Gene ◽  
Age Range ◽  
Prevalence Of Cancer

Background: Increasing evidence suggests that Duchenne muscular dystrophy (DMD) gene is involved in the occurrence of different types of cancer. Moreover, development of sarcomas was reported in mdx mice, the murine model of DMD, in older age. So far, nine isolated DMD patients were reported with concomitant cancer, four of whom with rhabdomyosarcoma (RMS), but no systematic investigation was performed about the true incidence of cancer in DMD. Methods: All members of the Italian Association of Myology were asked about the occurrence of cancer in their DMD patients in the last 30 years. Results: Four DMD patients with cancer were reported after checking 2455 medical records. One developed brain tumour at the age of 35 years. Two patients had alveolar RMS at 14 and 17 years of age. The fourth patient had a benign enchondroma when 11-year-old. Conclusion: Prevalence of cancer in general in the Italian DMD patients does not seem to be different from that in the general population with the same age range. Although the small numbers herein presented do not allow definitive conclusion, the frequent occurrence of RMS in DMD patients raises an alert for basic researchers and clinicians. The role of DMD gene in cancer merits further investigations.

Membrane Homeostasis: The Role of Actin Cytoskeleton

2021 ◽  
Vol 101 (1) ◽  
pp. 81-95
Author(s):  
Arikta Biswas ◽  
Rinku Kumar ◽  
Bidisha Sinha
Keyword(s):  
Actin Cytoskeleton

scholarly journals Anatomy and Neural Pathways Modulating Distinct Locomotor Behaviors in Drosophila Larva

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 90
Author(s):  
Swetha B. M. Gowda ◽  
Safa Salim ◽  
Farhan Mohammad
Keyword(s):  
Motor Neurons ◽  
Model Systems ◽  
Neural Pathways ◽  
Animal Movements ◽  
Drosophila Larvae ◽  
The Central Nervous System ◽  
Drosophila Larva ◽  
Locomotor Behaviors ◽  
Basic Level

The control of movements is a fundamental feature shared by all animals. At the most basic level, simple movements are generated by coordinated neural activity and muscle contraction patterns that are controlled by the central nervous system. How behavioral responses to various sensory inputs are processed and integrated by the downstream neural network to produce flexible and adaptive behaviors remains an intense area of investigation in many laboratories. Due to recent advances in experimental techniques, many fundamental neural pathways underlying animal movements have now been elucidated. For example, while the role of motor neurons in locomotion has been studied in great detail, the roles of interneurons in animal movements in both basic and noxious environments have only recently been realized. However, the genetic and transmitter identities of many of these interneurons remains unclear. In this review, we provide an overview of the underlying circuitry and neural pathways required by Drosophila larvae to produce successful movements. By improving our understanding of locomotor circuitry in model systems such as Drosophila, we will have a better understanding of how neural circuits in organisms with different bodies and brains lead to distinct locomotion types at the organism level. The understanding of genetic and physiological components of these movements types also provides directions to understand movements in higher organisms.

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