title: Thin filaments elongate from their pointed ends during myofibril assembly in Drosophila indirect flight muscle.
abstract: Tropomodulin (Tmod) is an actin pointed-end capping protein that regulates actin dynamics at thin filament pointed ends in striated muscle. Although pointed-end capping by Tmod controls thin filament lengths in assembled myofibrils, its role in length specification during de novo myofibril assembly is not established. We used the Drosophila Tmod homologue, sanpodo (spdo), to investigate Tmod's function during muscle development in the indirect flight muscle. SPDO was associated with the pointed ends of elongating thin filaments throughout myofibril assembly. Transient overexpression of SPDO during myofibril assembly irreversibly arrested elongation of preexisting thin filaments. However, the lengths of thin filaments assembled after SPDO levels had declined were normal. Flies with a preponderance of abnormally short thin filaments were unable to fly. We conclude that: (a) thin filaments elongate from their pointed ends during myofibril assembly; (b) pointed ends are dynamically capped at endogenous levels of SPDO so as to allow elongation; (c) a transient increase in SPDO levels during myofibril assembly converts SPDO from a dynamic to a permanent cap; and (d) developmental regulation of pointed-end capping during myofibril assembly is crucial for specification of final thin filament lengths, myofibril structure, and muscle function.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mardahl-Dumesnil
authors.forename: V M
authors.initials: VM
authors.lastname: Fowler
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D005426:Flight, Animal; D015870:Gene Expression / Q000502:physiology; D007536:Isomerism; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism* / Q000648:ultrastructure; D051348:Tropomodulin; D014714:Vertebrates
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D051348:Tropomodulin; C112833:spdo protein, Drosophila