Leiomodins: Larger Members of the Tropomodulin (Tmod) Gene Family

Conley, Catharine A.; Fritz-Six, Kimberly L.; Almenar-Queralt, Angels; Fowler, Velia M.

doi:10.1006/geno.2000.6501

Cited by 119 publications

(176 citation statements)

References 25 publications

Supporting

Mentioning

167

Contrasting

Order By: Relevance

“…Tmod1 is expressed predominantly in terminally differentiated, postmitotic cells (such as erythrocytes, lens fiber cells, neurons, and striated muscle), Tmod2 is expressed exclusively in neuronal tissues, Tmod3 is expressed ubiquitously, and Tmod4 is restricted to skeletal muscle in mammals (Fowler, 1987(Fowler, , 1990Sung et al, 1992;Watakabe et al, 1996;AlmenarQueralt et al, 1999b;Cox and Zoghbi, 2000;Conley et al, 2001). With these expression patterns, Tmod1, -3, and -4 are all potential regulators of pointed-end actin dynamics and thin filament lengths in skeletal muscle sarcomeres.…”

Section: Tmod1 Is Dispensable For Skeletal Muscle Development Myofibmentioning

confidence: 99%

“…9, A and B), leading us to believe that a faster fiber phenotype might also be present. Therefore, we used myosin ATPase staining to determine the inventories and the expression of nebulette versus nebulin in cardiac and skeletal muscle, respectively, may underlie these features of cardiac versus skeletal myofibril assembly (Moncman and Wang, 1995;Millevoi et al, 1998;Almenar-Queralt et al, 1999b;Cox and Zoghbi, 2000;Conley et al, 2001;Ono et al, 2005).…”

Section: Deletion Of Tmod1 Produces Fast Fiber Hypertrophymentioning

confidence: 99%

See 1 more Smart Citation

Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

Gokhin¹,

Lewis²,

McKeown³

et al. 2010

J Gen Physiol

Self Cite

View full text Add to dashboard Cite

Section: Tmod1 Is Dispensable For Skeletal Muscle Development Myofibmentioning

confidence: 99%

Section: Deletion Of Tmod1 Produces Fast Fiber Hypertrophymentioning

confidence: 99%

Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

Gokhin¹,

Lewis²,

McKeown³

et al. 2010

J Gen Physiol

Self Cite

View full text Add to dashboard Cite

“…Rather, an autosomal recessive inherited subtype of MMIHS has been discovered involving a homozygous nonsense mutation in Leiomodin1 (LMOD1), an understudied smooth muscle-restricted gene (11) that is a direct target of the Significance Rare recessive monogenic diseases are often found in isolated populations. In one such population, we identified a child carrying a homozygous nonsense mutation in an understudied smooth muscle-restricted gene called Leiomodin1 (LMOD1).…”

mentioning

confidence: 99%

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Halim

Wilson

Oliver

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

108

View full text Add to dashboard Cite

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting a recessive origin of the disease also exists. Using combined homozygosity mapping and whole exome sequencing, a genetically isolated family was found to carry a premature termination codon in Leiomodin1 (LMOD1), a gene preferentially expressed in vascular and visceral smooth muscle cells. Parents heterozygous for the mutation exhibited no abnormalities, but a child homozygous for the premature termination codon displayed symptoms consistent with MMIHS. We used CRISPR-Cas9 (CRISPR-associated protein) genome editing of Lmod1 to generate a similar premature termination codon. Mice homozygous for the mutation showed loss of LMOD1 protein and pathology consistent with MMIHS, including late gestation expansion of the bladder, hydronephrosis, and rapid demise after parturition. Loss of LMOD1 resulted in a reduction of filamentous actin, elongated cytoskeletal dense bodies, and impaired intestinal smooth muscle contractility. These results define LMOD1 as a disease gene for MMIHS and suggest its role in establishing normal smooth muscle cytoskeletal–contractile coupling.

show abstract

“…Recent studies have uncovered actin nucleation activities of the nebulin-N-WASP complex (9) and of formin proteins FHOD3 (10)(11)(12), mDia2, DAAM, FMNL1, and FMNL2 (13,14) in sarcomeres. In particular, leiomodin (Lmod) has been identified as a class of potent tandem-G-actin-binding nucleators in muscle cells (15,16); Lmod1 is found in smooth muscle of many human tissues, and Lmod2 and Lmod3 are found in cardiac and skeletal muscle (17). Lmod2 knockdown severely compromises sarcomere organization and assembly in muscle cells (15), whereas mutations, deletions (18), or instability (19) in Lmod3 underlies severe, often lethal, human nemaline myopathy.…”

mentioning

confidence: 99%

Mechanisms of leiomodin 2-mediated regulation of actin filament in muscle cells

Chen

Kondrashkina

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Leiomodin (Lmod) is a class of potent tandem-G-actin-binding nucleators in muscle cells. Lmod mutations, deletion, or instability are linked to lethal nemaline myopathy. However, the lack of highresolution structures of Lmod nucleators in action severely hampered our understanding of their essential cellular functions. Here we report the crystal structure of the actin-Lmod2 162-495 nucleus. The structure contains two actin subunits connected by one Lmod2 162-495 molecule in a non-filament-like conformation. Complementary functional studies suggest that the binding of Lmod2 stimulates ATP hydrolysis and accelerates actin nucleation and polymerization. The high level of conservation among Lmod proteins in sequence and functions suggests that the mechanistic insights of human Lmod2 uncovered here may aid in a molecular understanding of other Lmod proteins. Furthermore, our structural and mechanistic studies unraveled a previously unrecognized level of regulation in mammalian signal transduction mediated by certain tandem-G-actin-binding nucleators.actin nucleation | nemaline myopathy | pointed-end elongation

show abstract

Leiomodins: Larger Members of the Tropomodulin (Tmod) Gene Family

Cited by 119 publications

References 25 publications

Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Mechanisms of leiomodin 2-mediated regulation of actin filament in muscle cells

Contact Info

Product

Resources

About