Abstract
Phosphoinositides (PIPs) and their regulatory enzymes are key players in many cellular processes and are required for aspects of vertebrate development. Dysregulated PIP metabolism has been implicated in several human diseases, including a subset of skeletal myopathies that feature structural defects in the triad. The role of PIPs in skeletal muscle formation, and particularly triad biogenesis, has yet to be determined. CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) catalyzes the formation of phosphatidylinositol, which is the base of all PIP species. Loss of CDIPT should, in theory, result in the failure to produce PIPs, and thus provide a strategy for establishing the requirement for PIPs during embryogenesis. In this study, we generated cdipt mutant zebrafish and determined the impact on skeletal myogenesis. Analysis of cdipt mutant muscle revealed no apparent global effect on early muscle development. However, small but significant defects were observed in triad size, with T-tubule area, inter terminal cisternae distance and gap width being smaller in cdipt mutants. This was associated with a decrease in motor performance. Overall, these data suggest that myogenesis in zebrafish does not require de novo PIP synthesis but does implicate a role for CDIPT in triad formation.
Highlights
The primary function of skeletal muscle is to produce the force that initiates and controls movement
To investigate the role of PIPs in muscle development, we developed and characterized a new cdipt mutant zebrafish
We hypothesize that this modest phenotype is the result of PI deposited in the muscle during embryogenesis that provides sufficient substrate for generation and maintenance of PIP species at subsequent developmental stages
Summary
The primary function of skeletal muscle is to produce the force that initiates and controls movement. Muscle has a number of unique substructures that are dedicated to force production, including the sarcomere, the neuromuscular junction (NMJ) and the triad [1]. As our understanding of the molecular basis of human muscle diseases grows, it is becoming more apparent that many myopathies involve alterations to at least one of these structures [1,2,3]. Of increasing significance are the abnormalities in the structure and function of the triad, which. Role of CDIPT in zebrafish skeletal myogenesis figshare.
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