title: Muscle length and myonuclear position are independently regulated by distinct Dynein pathways.
abstract: Various muscle diseases present with aberrant muscle cell morphologies characterized by smaller myofibers with mispositioned nuclei. The mechanisms that normally control these processes, whether they are linked, and their contribution to muscle weakness in disease, are not known. We examined the role of Dynein and Dynein-interacting proteins during Drosophila muscle development and found that several factors, including Dynein heavy chain, Dynein light chain and Partner of inscuteable, contribute to the regulation of both muscle length and myonuclear positioning. However, Lis1 contributes only to Dynein-dependent muscle length determination, whereas CLIP-190 and Glued contribute only to Dynein-dependent myonuclear positioning. Mechanistically, microtubule density at muscle poles is decreased in CLIP-190 mutants, suggesting that microtubule-cortex interactions facilitate myonuclear positioning. In Lis1 mutants, Dynein hyperaccumulates at the muscle poles with a sharper localization pattern, suggesting that retrograde trafficking contributes to muscle length. Both Lis1 and CLIP-190 act downstream of Dynein accumulation at the cortex, suggesting that they specify Dynein function within a single location. Finally, defects in muscle length or myonuclear positioning correlate with impaired muscle function in vivo, suggesting that both processes are essential for muscle function.
authors.affiliation: Program in Developmental Biology, Sloan Kettering Institute, New York, NY 10065,  USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Folker
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Schulman
authors.forename: Mary K
authors.initials: MK
authors.lastname: Baylies
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000502:physiology*; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000648:ultrastructure; D024510:Muscle Development; D009132:Muscles / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018797:Cell Cycle Proteins; C105393:DCTN1-p150 protein, Drosophila; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; C513192:Lis-1 protein, Drosophila; D008869:Microtubule-Associated Proteins; C405164:Pins protein, Drosophila; C110769:cytoplasmic linker protein 190; D004398:Dyneins