The superfast extraocular myosin (MYH13) is localized to the innervation zone in both the global and orbital layers of rabbit extraocular muscle

2002 ◽  
Vol 205 (20) ◽  
pp. 3133-3142 ◽  
Author(s):  
Margaret M. Briggs ◽  
Fred Schachat

SUMMARY Extraocular muscles (EOMs) are the most molecularly heterogeneous and physiologically diverse mammalian striated muscles. They express the entire array of striated muscle myosins, including a specialized myosin heavy chain MYH13, which is restricted to extraocular and laryngeal muscles. EOMs also exhibit a breadth of contractile activity, from superfast saccades to slow tracking and convergence movements. These movements are accomplished by the action of six ultrastructurally defined fiber types that differ from the type IIa, IIb, IIx and I fibers found in other skeletal muscles. Attempts to associate different eye movements with either the expression of different myosins or the activity of particular EOM fiber types are complicated by the molecular heterogeneity of several of the fiber types, and by electromyography studies showing that the majority of extraocular motor units participate in both fast and slow eye movements. To better understand the role of MYH13 in ocular motility, we generated MYH13-sequence-specific antibodies and used SDS-PAGE to quantify the regional distribution of myosin in EOM and to characterize its heterogeneity in single fibers. These studies demonstrate that MYH13 is preferentially expressed in the majority of orbital and global fibers in the central innervation zone of rabbit EOM. Many individual fibers express MYH13 with the fast IIb myosin and varying amounts of IIx myosin. The differential localization of MYH13, coupled with specialization of the sarcoplasmic reticulum and thin filament systems, probably explains how activation of the endplate band region enables the majority of EOM fibers to contribute to superfast contractions.

1989 ◽  
Vol 37 (4) ◽  
pp. 447-454 ◽  
Author(s):  
B K Grove ◽  
L Cerny ◽  
J C Perriard ◽  
H M Eppenberger ◽  
L E Thornell

The functions of two myofibrillar proteins, myomesin (Mr 185,000) and M-protein (Mr 165,000), associated with the M-band are as yet unknown. To extend our knowledge of these proteins, we have examined chicken striated muscles with fast and slow contractile properties, e.g., pectoralis major, PLD, ALD, medial adductor, and lateral adductor, to determine the expression and isoform composition of myomesin and M-protein in various muscles and fiber types. The high molecular weight M-band proteins were characterized and quantitated using monoclonal antibodies in immunoblotting and double-antibody sandwich ELISA. Fiber specificity was determined by immuno- and enzyme histochemistry. In addition to the previously reported Mr 195,000 and 190,000 isoforms of myomesin in heart [Grove et al. (1985): J Cell Biol 101:1431], the Mr 185,000 myomesin in skeletal muscles may represent different isoforms in fast and slow muscles on the basis of distinctive degradation patterns. M-protein has the same molecular weight in striated chicken muscles and degradation patterns indicate only one isoform. The low quantities of M-protein in slow muscles were shown to be due to the absence of M-protein in two of the generally recognized slow fiber types, types I and III. Thus, M-protein was present only in fast type II fibers, whereas myomesin was ubiquitous in all fiber types. Whatever the causal relationship, M-protein appears to function in fast motor units composed of type II fibers.


Author(s):  
Ayse Gul Kocak Altintas ◽  
Ayse Gul Kocak Altintas

Duane retraction syndrome is the most frequently seen restrictive ocular motility disorders. It is clinically presented with limitation of horizontal movement, variable amounts of upshoots or downshoots and globe retraction combined with narrowing of the palpebral aperture on attempted adduction. An 8-year-old patient presented with severe restriction of abduction, reciprocal upshots or downshoots, and globe retraction combined with the palpebral fissure narrowing of on adduction. After the modified Y splitting of LR and recession of both horizontal rectus operation, all cosmetically disfiguring clinical features disappeared. In this case report modified Y splitting procedure and its long-term efficacy is presented.


2002 ◽  
Vol 205 (15) ◽  
pp. 2189-2201 ◽  
Author(s):  
Fred Schachat ◽  
Margaret M. Briggs

SUMMARY Extraocular muscle exhibits higher-velocity and lower-tension contractions than other vertebrate striated muscles. These distinctive physiological properties are associated with the expression of a novel extraocular myosin heavy chain (MYH). Encoded by the MYH13 gene, the extraocular myosin heavy chain is a member of the fast/developmental MYH gene cluster on human chromosome 17 and the syntenic MYH cluster on mouse chromosome 11. Comparison of cDNA sequences reveals that MYH13 also encodes the atypical MYH identified in laryngeal muscles, which have similar fast contractile properties. Comparing the MYH13 sequence with the other members of the fast/developmental cluster, the slow/cardiac MYH genes and two orphan skeletal MYH genes in the human genome provides insights into the origins of specialization in striated muscle myosins. Specifically, these studies indicate (i) that the extraocular myosin is not derived from the adult fast skeletal muscle myosins, but was the first member of the fast/developmental MYH gene cluster to diverge and specialize, (ii) that the motor and rod domains of the MYH13 have evolved under different selective pressures and (iii) that the MYH13 gene has been largely insulated from genomic events that have shaped other members of the fast/developmental cluster. In addition, phylogenetic footprinting suggests that regulation of the extraocular MYH gene is not governed primarily by myogenic factors, but by a hierarchical network of regulatory factors that relate its expression to the development of extraocular muscles.


1990 ◽  
Vol 259 (4) ◽  
pp. E593-E598 ◽  
Author(s):  
E. J. Henriksen ◽  
R. E. Bourey ◽  
K. J. Rodnick ◽  
L. Koranyi ◽  
M. A. Permutt ◽  
...  

The relationships among fiber type, glucose transporter (GLUT-4) protein content, and glucose transport activity stimulated maximally with insulin and/or contractile activity were studied by use of the rat epitrochlearis (15% type I-20% type II2a-65% type IIb), soleus (84-16-0%), extensor digitorum longus (EDL, 3-57-40%), and flexor digitorum brevis (FDB, 7-92-1%) muscles. Insulin-stimulated 2-deoxy-D-glucose (2-DG) uptake was greatest in the soleus, followed (in order) by the FDB, EDL, and epitrochlearis. On the other hand, contractile activity induced the greatest increase in 2-DG uptake in the FDB, followed by the EDL, soleus, and epitrochlearis. The effects of insulin and contractile activity on 2-DG uptake were additive in all the muscle preparations, with the relative rates being FDB greater than soleus greater than EDL greater than epitrochlearis. Quantitation of the GLUT-4 protein content with the antiserum R820 showed the following pattern: FDB greater than soleus greater than EDL greater than epitrochlearis. Linear regression analysis showed that whereas a relatively low and nonsignificant correlation existed between GLUT-4 protein content and 2-DG uptake stimulated by insulin alone, significant correlations existed between GLUT-4 protein content and 2-DG uptake stimulated either by contractions alone (r = 0.950) or by insulin and contractions in combination (r = 0.992). These results suggest that the differences in maximally stimulated glucose transport activity among the three fiber types may be related to differences in their content of GLUT-4 protein.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Glenda Comai ◽  
Eglantine Heude ◽  
Sebastian Mella ◽  
Sylvain Paisant ◽  
Francesca Pala ◽  
...  

In most vertebrates, the upper digestive tract is composed of muscularized jaws linked to the esophagus that permits food ingestion and swallowing. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we show that the transcription factors Tbx1 and Isl1 are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies point to MET/HGF signaling for antero-posterior migration of esophagus muscle progenitors, where Hgf ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Our findings establish a Tbx1-Isl1-Met genetic hierarchy that uniquely regulates esophagus myogenesis and identify distinct genetic signatures that can be used as framework to interpret pathologies arising within CPM derivatives.


Development ◽  
2000 ◽  
Vol 127 (10) ◽  
pp. 2041-2051 ◽  
Author(s):  
A.K. Corsi ◽  
S.A. Kostas ◽  
A. Fire ◽  
M. Krause

The basic helix-loop-helix (bHLH) transcription factor Twist plays a role in mesodermal development in both invertebrates and vertebrates. In an effort to understand the role of the unique Caenorhabditis elegans Twist homolog, hlh-8, we analyzed mesodermal development in animals with a deletion in the hlh-8 locus. This deletion was predicted to represent a null allele because the HLH domain is missing and the reading frame for the protein is disrupted. Animals lacking CeTwist function were constipated and egg-laying defective. Both of these defects were rescued in transgenic mutant animals expressing wild-type hlh-8. Observing a series of mesoderm-specific markers allowed us to characterize the loss of hlh-8 function more thoroughly. Our results demonstrate that CeTwist performs an essential role in the proper development of a subset of mesodermal tissues in C. elegans. We found that CeTwist was required for the formation of three out of the four non-striated enteric muscles born in the embryo. In contrast, CeTwist was not required for the formation of the embryonically derived striated muscles. Most of the post-embryonic mesoderm develops from a single lineage. CeTwist was necessary for appropriate patterning in this lineage and was required for expression of two downstream target genes, but was not required for the expression of myosin, a marker of differentiation. Our results suggest that mesodermal patterning by Twist is an evolutionarily conserved function.


Author(s):  
R. John Leigh ◽  
David S. Zee

This chapter reviews (with illustrative videos) disorders of gaze in diseases involving the basal ganglia, including Parkinson’s disease, progressive supranuclear palsy (PSP), hyperkinetic movement syndromes such as oculogyric crisis, and Huntington’s disease. Ocular motor syndromes caused by lesions in the cerebral hemispheres are discussed, including gaze deviations. Distinctive features of ocular motor apraxia, both acquired and congenital, are highlighted. Eye movements during epilepsy, and abnormal eye movements in patients with dementia, including Alzheimer’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis are reviewed. Eye movement disorders in psychiatric illnesses, including schizophrenia, bipolar affective disorder, and autism are summarized. Eye movements in stupor and coma are discussed. The range of ocular motor disturbances in multiple sclerosis (MS) is reviewed as well as the ocular motor manifestations of metabolic and deficiency disorders, including Niemann-Pick disease, Tay-Sachs disease, Gaucher’s disease, and Wernicke’s encephalopathy. Disorders of eye movements induced by drugs or toxins are tabulated.


Author(s):  
R. John Leigh ◽  
David S. Zee

This chapter reviews contributions of orbital tissues and extraocular muscles (EOM) to the control of eye movements. The anatomy of the orbit, fascia, fibromuscular pulleys, and EOM are described and related to the kinematics of 3-D eye rotations. Current concepts of the embryology of the EOM and their unique and diverse characteristics are described, suggesting why they are more vulnerable to certain neuromuscular disorders and less susceptible to others, compared with skeletal muscles. Electrophysiological properties of different EOM fiber types (and their motor neuron innervation) are contrasted, describing new models that attempt to account for nonlinear mechanical properties of the orbit. The substrate and roles of extraocular proprioception in the control of eye movements are summarized and related to clinical disorders affecting EOM. The anatomy of the cranial nerves supplying the EOM is summarized, diagrammed and highlighted to aid diagnosis of common palsies of the oculomotor, trochlear, and abducens nerves.


2011 ◽  
Vol 25 (1) ◽  
pp. 9 ◽  
Author(s):  
Gabriela Marini ◽  
Angélica M. Pascon Barbosa ◽  
Débora C. Damasceno ◽  
Selma M. Michelin Matheus ◽  
Rodrigo De Aquino Castro ◽  
...  

<em>Background</em>. This study was undertaken to test the hypothesis that diabetes and pregnancy detrimentally affect the normal function of urethral striated muscles in rats, providing a model for additional studies related to urinary incontinence. The aim of this study was to evaluate morphological alterations in the urethral striated muscles of diabetic pregnant rats. <em>Design and methods. </em>Twenty female Wistar rats were distributed into four experimental groups of five rats as follows: virgin, pregnant, diabetic virgin, and diabetic pregnant. Diabetes was induced using streptozotocin administration (40 mg/kg i.v.). The rats were lethally anesthetized, and the urethra and vagina were extracted as a unit. Cryostat sections (6 µm thick) were cut and stained with hematoxylin-eosin, and immunohistochemical procedures were performed and subjected to morphological and semi quantitative analysis. <em>Results</em>. The urethral striated muscle from the diabetic pregnant rats presented with the following variations: thinning and atrophy, disorganization and disruption associated with the colocalization of fast and slow fibers and a steady decrease in the proportion of fast <em>vs</em> slow fibers. <em>Conclusion</em>. Diabetes and pregnancy impair the urethral striated muscle and alter its fiber type distribution.


2020 ◽  
Vol 133 (15) ◽  
pp. jcs243162
Author(s):  
Kristen K. Bjorkman ◽  
Martin G. Guess ◽  
Brooke C. Harrison ◽  
Michael M. Polmear ◽  
Angela K. Peter ◽  
...  

ABSTRACTStriated muscle is a highly specialized collection of tissues with contractile properties that vary according to functional needs. Although muscle fiber types are established postnatally, lifelong plasticity facilitates stimulus-dependent adaptation. Functional adaptation requires molecular adaptation, which is partially provided by miRNA-mediated post-transcriptional regulation. miR-206 is a muscle-specific miRNA enriched in slow muscles. We investigated whether miR-206 drives the slow muscle phenotype or is merely an outcome. We found that miR-206 expression increases in both physiological (including female sex and endurance exercise) and pathological conditions (muscular dystrophy and adrenergic agonism) that promote a slow phenotype. Consistent with that observation, the slow soleus muscle of male miR-206-knockout mice displays a faster phenotype than wild-type mice. Moreover, left ventricles of male miR-206 knockout mice have a faster myosin profile, accompanied by dilation and systolic dysfunction. Thus, miR-206 appears to be necessary to enforce a slow skeletal and cardiac muscle phenotype and to play a key role in muscle sexual dimorphisms.


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